Biomedical subjects

E Clonfero

Publications and source records attributed to E Clonfero.

At least 19 recordsLinked to original sources

PubMed2004

Non-smoking coke oven workers show an occupational PAH exposure-related increase in urinary mutagens.

We examined the urinary mutagenicity in the YG1024 Salmonella typhimurium strain in the presence of S9 mix, of 31 male non-smoking coke oven workers and an equal number of controls matched for gender and dietary habits. Occupational PAH exposure to the workers was assessed by means of the individual urinary post-shift excretion of 1-pyrenol (mean +/- S.D.: 5.41 +/- 6.06 micromole/mol creatinine). Eleven urinary extracts of workers (35.5%) were clearly mutagenic (with at least a doubling of the number of spontaneous revertants), against only two samples in the control group (6.5%) (chi2-test; chi2 = 7.883; P < 0.01). Moreover, the mean mutagenic activity level corrected for dilution/concentration of the urine was about three times higher in coke oven workers than in matched controls (mean +/- S.D. (range) 495 +/- 407 (89.7-1603) versus 186 +/- 113 (14.2-524) net revertants/mmol creatinine; Mann-Whitney U-test, z = 3.86, P < 0.001). Simple linear regression analysis showed that the coke workers' urinary mutagenic activity is associated with the PAH occupation-related urinary excretion of 1-pyrenol (r = 0.41, P = 0.0215). This study definitely demonstrates an occupation-related exposure of coke oven workers' bladder epithelium to mutagenic PAH metabolites. This factor, mainly in the case of high exposure studied here, may account for a higher bladder cancer risk in coke oven workers.

Coke↗

PubMed2002

Role of metabolic polymorphisms NAT2 and CYP1A2 on urinary mutagenicity after a pan-fried hamburger meal.

In this work the phenotyping approach was used to study the influence of metabolic polymorphisms NAT2 and CYP1A2 on S9-mediated urinary mutagenicity, detected with Salmonella strain YG1024, in 50 subjects after a meal of pan-fried hamburgers. All 50 post-meal samples, but not pre-meal ones, were clearly mutagenic (number of urine samples able to double number of spontaneous revertants was 50 to 0, respectively). CYP1A2 positively influences urinary mutagenicity: a rise in CYP1A2 activity increases levels of post-meal urinary mutagens (1.16+/-0.91 vs 1.72+/-1.19 7-h minimum mutagenic doses (MMDs)/intake), especially in NAT2 slow acetylators (2.18+/-1.33 vs 0.90+/-0.54 7-h MMDs/intake, Mann-Whitney U-test, P<0.05). NAT2 rapid acetylators exert lower post-meal urinary mutagenicity than slow ones (1.41+/-1.02 vs 1.77+/-2.45 7-h MMDs/intake) and even more if the latter are extensive CYP1A2 metabolizers (1.41+/-1.02 vs 2.18+/-1.33 7-h MMDs/intake), but the difference did not reach statistical significance. In conclusion, this study indicates that CYP1A2 and NAT2 activities influence the presence of urinary mutagens after a meal of pan-fried hamburger (rich in HHAs) and consequently their potential genotoxic risk.

Adult↗

PubMed2000

Biological indicators of genotoxic risk and metabolic polymorphisms.

International scientific publications on the influence of metabolic genotypes on biological indicators of genotoxic risk in environmental or occupational exposure are reviewed. Biomarkers of exposure (substance or its metabolites in biological fluids, urinary mutagenicity, protein and DNA adducts) and of effects (chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (Mn), COMET assay, HPRT mutants) have been evaluated according to different genotypes (or phenotypes) of several activating/detoxifying metabolic activities. In less than half the studies (43 out of 95), the influence of genotype on the examined biological indicator was found, of which four report poorly reliable results (i.e., with scarce biological plausibility, because of the inconsistency of modulated effect with the type of enzymatic activity expressed). As regards urinary metabolites, the excretion of mercapturic acids (MA) is greater in subjects with high GST activity, that of 1-pyrenol and other PAH metabolites turns out to be significantly influenced by genotypes CYP1A1 or GSTM1 null, and that of exposure indicators to aromatic amines (AA) (acetylated and non-acetylated metabolites) is modulated by NAT2. In benzene exposure, preliminary results suggest an increase in urinary t, t-muconic acid (t,t-MA) in subjects with some genotypes. On urinary mutagenicity of PAH-exposed subjects, the effects of genotype GSTM1 null, alone or combined with NAT2 slow are reported. When DNA adduct levels are clearly increased in PAH-exposed group (18 out of 22), 7 out of 18 studies report the influence of GSTM1 null on this biomarker, and of the five studies which also examined genotype CYP1A1, four report the influence of genotype CYP1A1, alone or in combination with GSTM1 null. A total of 25 out of 41 publications (61%) evaluating the influence of metabolic polymorphisms on biomarkers of effect (cytogenetic markers, COMET assay, HPRT mutants) do not record any increase in the indicator due to exposure to the genotoxic agents studied, confirming the scarce sensitivity of these indicators (mainly HPRT mutants, Mn, COMET assay) for assessing environmental or occupational exposure to genotoxic substances. Concluding, in determining urinary metabolites for monitoring exposure to genotoxic substances, there is sufficient evidence that genetically-based metabolic polymorphisms must be taken into account in the future. The unfavourable association for the activating/detoxifying metabolism of PAH is also confirmed as a risk factor due to the formation of PAH-DNA adducts. The clearly protective role played by GSTT1 on DEB (and/or related compound)-induced sister chromatid exchanges (SCEs) should be noted. The modulating effects of genotypes on protein adduct levels in environmental and occupational exposure have not yet been documented, and most studies on the influence of genotype on biological indicators of early genotoxic effects report negative results.

Animals↗

PubMed1999

Influence of GSTM1, GSTT1, GSTP1, and EPHX gene polymorphisms on DNA adduct level and HPRT mutant frequency in coke-oven workers.

To evaluate the influence of individual susceptibility factors on the level of polyaromatic (PAH) hydrocarbon DNA adducts and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutants in peripheral lymphocytes, 70 coke-oven workers exposed to PAH were genotyped for four metabolic enzyme polymorphisms of potential importance in PAH metabolism. The examined genetic polymorphisms concerned glutathione S-transferases M1 (GSTM1; gene deletion; 96 workers), T1 (GSTT1; gene deletion), P1 (GSTP1; Ile-->Val substitution at codon 104 or Ile-->Val at codon 104 and Val-->Ala at codon 113), and microsomal epoxide hydrolase (EPHX; Tyr-->His substitution at codon 113 and His-->Arg at codon 139). The workers were classified in a high- and low-exposure group on the basis of urinary concentration of 1-pyrenol. The GSTM1 null genotype increased the number of DNA adducts in smoking coke-oven workers with high PAH exposure. DNA adducts were affected by PAH-exposure in non-smokers and in GSTM1 null smokers and by smoking in GSTM1 null individuals. In a multiple linear regression analysis, the interaction of the GSTM1 genotype was statistically significant (p = 0.04) with smoking (yes/no) and of borderline significance (p = 0.06) with PAH-exposure (high/low). As smoking also increased urinary 1-pyrenol, the genotype modification seemed to concern DNA adducts due to smoking rather than occupational exposure. GSTT1 positive individuals showed an elevated level of DNA adducts in comparison with GSTT1 null subjects (p = 0.04), and EPHX genotypes associated with slow hydroxylation reaction yielded a higher (p = 0.05) HPRT mutant frequency than fast EPHX genotypes; these findings were, however, based on small numbers of subjects and need to be clarified in further studies. In conclusion, our findings indicate that homozygous deletion of GSTM1 results in an increased sensitivity to genotoxic PAHs in tobacco smoke, which is seen as an increase in aromatic DNA adducts in blood mononuclear cells.

Adult↗

PubMed1999

Influence of metabolic genotype GSTM1 on levels of urinary mutagens in patients treated topically with coal tar.

Fifteen hospitalized, non-smoking, dermatological patients were treated with ointment containing 2% coal tar (CT) in order to assess the influence of metabolic genotype GSTM1 on urinary mutagen levels. Urinary 1-pyrenol, the main metabolite of pyrene, was used to check the high exposure to PAH of this population. The mean levels of urinary 1-pyrenol found in the 24-h urine of our patients were 467. 8+/-211.0 nmoles-24 h (range 94.6-890.1 nmoles-24 h). Mutagenicity was assessed on urine samples collected over a period of 24 h, after three consecutive days of topical application, using the bacterial mutagenesis test on Salmonella typhimurium strains TA98 and YG1024 in the presence of microsomal enzymes. The latter strain turned out to be more sensitive than the former in revealing urinary mutagens in these patients (42 693+/-30 867 vs. 6877+/-6040 net revertants-24 h). The mutagenicity on YG1024 strain and 1-pyrenol levels of urine samples were correlated (Spearman's rank correlation coefficient=0. 6678, P<0.01, z=2.795). The influence of genotype GSTM1 on urinary mutagen levels was assessed on strain YG1024. The values of urinary mutagenicity of subjects with genotype GSTM1-null (n=6) were on average higher than those of GSTM1-positive subjects (n=9) (55 498+/-45 957 vs. 34 156+/-11 933 net rev.-24 h), a non-significant statistical difference. The mean total excretion of mutagens corrected for PAH exposure (net rev./nmoles of urinary 1-pyrenol) in GSTM1-null patients was double that of GSTM1-positive ones (136. 8+/-34.7 vs. 70.8+/-23.3 net rev./nmoles of urinary 1-pyrenol; one-tailed Mann-Whitney U-test, U=11.5, P<0.05). These results indicate a greater body burden of promutagens, resulting from skin application of CT, in GSTM1-null subjects.

Administration, Topical↗

PubMed1999

The influence of cytochrome P450 1A1 and glutathione S-transferase M1 genotypes on biomarker levels in coke-oven workers.

The present study has the aim of evaluating gene-environment interaction on the levels of different biomarkers in coke-oven workers exposed to PAH. In order to assess whether the levels of some biomarkers (PAH-DNA adducts, nitro-PAH adducts to Hb and MN frequency) could be modulated by the genetic metabolic polymorphisms for CYP1A1 and GSTM1, we analysed in 76 coke-oven workers and 18 controls the CYP1A1 (MspI and Ile/Val sites) and the GSTM1 genotypes by a PCR assay. In individuals with shared setup of CYP1A1 or GSTM1 genotypes, we analysed how the specified biomarkers correlated with total PAH exposure (urinary levels of 1-hydroxypyrene) both by a stratified analysis and logistic regression modelling. Statistically significant (P = 0.03 and P = 0.01) higher percentages of the more susceptible GSTM1- subjects compared to the GSTM1+ subjects and of the more susceptible CYP1A1 Ile/Val individuals compared to the CYP1A1 Ile/Ile individuals were detected for high levels of PAH-DNA adducts in the high exposure group (namely high levels of 1-OHP). A statistically significant association was observed between increased PAH-DNA adduct levels and the more susceptible GSTM1- genotype (P.O.R. = 4.18, P = 0.03) in a logistic regression modelling and a significant interaction between PAH exposure and GSTM1-genotype was found for PAH-DNA adducts. No effect of these metabolic genotypes was observed for MN frequency and nitro-PAH adducts to Hb. In conclusion, a gene-environment interaction between PAH exposure and two metabolic genotypes involved in activation (CYP1A1) and detoxification (GSTM1) of PAHs, respectively, has been identified.

Adult↗

PubMed1999

Influence of GSTM1 genotypes on anti-BPDE-DNA adduct levels in mononuclear white blood cells of humans exposed to PAH.

OBJECTIVE: Association between genetic deletion polymorphism of GSTM1 (*0/*0 or active) and levels of anti (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE)-DNA adducts in the peripheral blood lymphocyte plus monocyte fraction (LMF) of PAH-exposed subjects was investigated. METHODS: A total of 94 Caucasian subjects comprised the sample population: 13 coke-oven workers, 19 chimney sweeps, 36 aluminum-anode plant workers, and 26 non-occupationally PAH-exposed subjects (controls). PAH exposure was assessed in each group by means of the urinary excretion of 1-pyrenol (mean group levels 1.2, 0.7, 0.3, and 0.1 mumol/mol creatinine in coke-oven workers, chimney sweeps, aluminum-anode plant workers, and control subjects, respectively). Anti-BPDE-DNA adducts were detected by HPLC/fluorescence analysis of anti-BPDE tetrols (tetrol I-1) released after acid hydrolysis of DNA samples. RESULTS: In coke-oven workers the percentage of cases with adduct levels exceeding the 95th percentile control value (4.4 adducts/10(8) nucleotides) was significantly higher in the subgroup with the null GSTM1 genotype (*0/*0) (100%) than in that with active GSTM1 (43%; chi 2 test, P < 0.05). In the other groups with different and lower levels of PAH exposure the percentages of positive samples were always higher in the subgroup with GSTM1 *0/*0 than in the active one, although the differences were not statistically significant. Univariate (odds ratio) and multivariate (relative risk) analyses showed that the risk of having high anti-BPDE-DNA levels increased with occupational exposure to PAH. Such risks, moreover, were further significantly increased by the lack of GSTM1 activity (RR = 5.94; CI = 1.15-30.7; P < 0.05). In coke-oven workers, chimney sweeps, and aluminum workers, respectively, the multiplicative effect of the null genotype with occupational PAH exposure gives risks of 162 (= 27.2 x 5.94), 10 (= 1.70 x 5.94), and 3 (= 0.50 x 5.94) times higher probability (risk) of high BPDE-DNA adduct formation than that of non-exposed subjects with the active GSTM1 genotype. CONCLUSION: Our results indicate a greater risk of anti-BPDE-DNA adduct formation resulting from occupational high-level PAH-exposure in GSTM1 null (GSTM1 *0/*0) workers.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1999

HPLC/fluorescence determination of anti-BPDE-DNA adducts in mononuclear white blood cells from PAH-exposed humans.

The aim of this study was to compare (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE)-DNA adduct levels in groups of humans subjected to various levels of polycyclic aromatic hydrocarbon (PAH) (benzo[a]pyrene) exposure. An HPLC/fluorescence method was applied to detect specifically anti-BPDE-DNA adducts in mononuclear white blood cells [lymphocyte plus monocyte fraction (LMF)] from humans exposed to PAHs. A total of 130 subjects comprised the sample population: 26 psoriatic patients (3 days after clinical coal tar treatment of the skin), 15 coke oven workers, 19 chimney sweeps, 36 aluminium anode plant workers and 34 non-occupationally PAH-exposed subjects (controls). PAH exposure was assessed in each group by means of the urinary excretion of 1-pyrenol (mean group levels: 1.2, 0.7, 0.3, 65.0 and 0.1 micromol/mol creatinine in coke oven workers, chimney sweeps, aluminium plant anode workers, psoriatic patients and non-occupationally PAH-exposed subjects, respectively). HPLC/fluorescence analysis of BPDE-DNA adducts showed that the percentage of subjects with adduct levels exceeding the 95 percentile control subject value (8.9 adducts/10(8) nucleotides) was significantly high in coke oven workers (46.7%) and chimney sweeps (21.0%) (chi2 test, P < 0.01 and P < 0.05, respectively) but not in aluminium plant workers (11.1%) and psoriatic patients (0%). The increase in BPDE-DNA adduct levels in LMF (Ln values) was significantly related to chronic inhalatory and high PAH exposure (linear multiple regression analysis, F = 6.37, P < 0.01; t = 4.2, P < 0.001). Skin acute (or short-term) and high PAH exposure, charcoal-grilled meat consumption and smoking habit did not seem to influence BPDE-DNA adduct formation in LMF.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1998

Urinary mutagenicity on TA98 and YG1024 Salmonella typhimurium strains after a hamburger meal: influence of GSTM1 and NAT2 genotypes.

Mutagenicity on TA98 and YG1024 Salmonella typhimurium strains of pan-fried hamburger extracts and of 24 h post-meal urine from 32 non-smoking volunteers was evaluated. Each participant in the study was GSTM1 and NAT2 genotyped. After cooking the meat showed mutagenic activity (mean +/- SD) on strains TA98 and YG1024 of 114 +/- 129 and 1437 +/- 1536 net revertants/g respectively. Twenty three of 32 urine samples showed clear mutagenic activity (i.e. caused at least a doubling of the number of spontaneous revertants) on the O-acetyltransferase over-producing strain YG1024, while none of the post-meal 24 h urine samples was clearly mutagenic on strain TA98. Total 24 h post-meal YG1024-active urinary mutagens were well correlated with the levels of mutagen intake with the meal (r2 = 0.5977, F = 44.58, P < 0.01). In the group under study GSTM1 genotypes did not influence urinary mutagenicity. Highly exposed subjects (n = 15) with the NAT2-ss genotype showed significantly increased levels of urinary mutagenicity on strain YG1024 in comparison with NAT2-R subjects (mutagen intake-adjusted total 24 h mutagen excretion = 1.00 +/- 0.29 versus 0.66 +/- 0.32, Mann-Whitney U test, U = 12.5, P < 0.05). Our results suggest that the levels of urinary mutagens derived from diets rich in heterocyclic aromatic amines, which are specifically detected by the YG1024 Salmonella strain, are modulated by NAT2-dependent enzyme activity, slow acetylators having higher levels of mutagens in their urine. Subjects with the rapid acetylator genotype, who are known to be at risk for colon cancer, seem to be partially protected with respect to the risk of bladder cancer.

Animals↗

PubMed1996

Mutagenicity and contents of polycyclic aromatic hydrocarbons in used and recycled motor oils.

Thirteen samples of used motor oil and 33 recycled fractions, obtained in the laboratory by means of a recovery process similar to that currently used in Italy (vacuum distillation followed by thermal clay treatment) were examined. The Ames test (standard and modified version according to Blackburn) was used to determine the mutagenicity of the extracts and their contents of polyaromatic fraction (PAF) (IP346/80 method) and polycyclic aromatic hydrocarbons (PAH) (Grimmer's method). Used motor oils are mutagenic, both directly and indirectly. The highest values have been found in used oils from motor vehicles using leaded petrol (up to 118.8 revertants/mg). Samples from vehicles using unleaded petrol or diesel fuel are less mutagenic (up to 31.1 and 16.4 rev/mg, respectively). The enrichment in mutagens due to the use of oil in the three types of engine ranges from mean values of 6.2, 1.1 and 0.4 rev/mg per 1000 km, respectively. Recycled oils are almost completely devoid of direct mutagenic activity (33 samples: mean +/- SD = 1.6 +/- 1.5 rev/mg). Most recycled distillates show considerable mutagenic activity in the presence of microsomial enzymes (up to 82.5 rev/mg), although this is reduced with respect to the original oils (recycled, mean +/- SD = 13.8 +/- 15.5 rev/mg; original oils, mean +/- SD = 30.7 +/- 35.2, Mann-Whitney U-test, z = 1.793, p < 0.05). Both PAF and PAH contents are high in used oils from the two types of petrol engine but not in those from diesel engines. Recycling reduces PAF contents only in used oils from petrol engines, from a mean value of 13.91 +/- 7.32 to 4.23 +/- 2.90% (comparison with original used oils, Mann-Whitney U-test, U = 8, p < 0.01). The light distilled fractions have greater concentrations of indirect mutagens, PAF and PAH than the others. The increase in PAH in light recycled products with respect to the original used oils is significant (Wilcoxon's t-test, z = 2.306, p < 0.05). Benzo[a]pyrene (BaP) is found in appreciable quantities (> 10 ppm) in all used oils from petrol engines and in most of their recycled products. Recycling generally recovers 50% of mutagens and PAF and about 80% of PAH. Considered together, recycled products have in any case contents of mutagens and PAF which are significantly lower than those in the parent oils, but not of PAH (Wilcoxon's t-test; mutagens, z = 2.935, p < 0.01; PAF, z = 3.145, p < 0.01; PAH, z = 1.397, not significant). Lastly, many recycled oils have PAH concentrations which are equal to or higher than those of the original used oils. The health risks linked to professional exposure to these types of oils and the inadequate recycling process currently used (redistillation and thermal clay treatment) in reducing mutagenic and cancerogenic substances from used motor oils are stressed.

Fuel Oils↗

PubMed1996

GSTM1 and NAT2 genotypes and urinary mutagens in coke oven workers.

The influence of the metabolic genotypes GSTM1 and NAT2 on the urinary excretion of mutagens in 46 coke oven workers (27 of them smokers) was studied. Exposure to polycyclic aromatic hydrocarbons (PAH) was estimated from urinary 1-pyrenol levels, which varied from 0.23 to 5.59 micromol/mol creatinine. Fourteen urine samples (30.4%), all but one belonging to smokers, were positive for mutagenic activity (i.e. at least one of the assayed doses was able to double the number of spontaneous revertants). Nine of the urine-positive subjects were both GSTM1-null and NAT2-ss (64.3%), while the same combination of genotypes was found in nine out of 31 urine-negative subjects (29.0%) (P < 0.05). Significantly more smoking workers with the genotype combination GSTM1-null/NAT2-ss showed positive urine mutagenicity than the other subjects (75.0 versus 28.6%, P < 0.05). Smokers with the slow acetylator genotype showed a significantly higher frequency of positive urine samples than smoking fast acetylators (64.7 versus 22.2%, P < 0.05). Our results suggest that smoking coke oven workers with genotypes unfavourable for detoxification of aromatic amines (NAT2-ss) and PAH (GSTM1-null) may have an increased risk of developing bladder cancer.

Arylamine N-Acetyltransferase↗

PubMed1996

Excretion of mutagens, nicotine and its metabolites in urine of cigarette smokers.

Urine samples from 26 cigarette smokers on a restricted diet were collected in the late afternoon. Urine extracts on XAD-2 resin were tested for mutagenicity in the microsuspension assay using Salmonella typhimurium strain TA98 in the presence of metabolizing and deconjugating enzymes. Levels of urinary nicotine plus metabolites and cotinine were determined. Eighteen samples were clearly mutagenic, i.e. capable of doubling the number of spontaneous revertants at one of the assayed doses of urine. Urinary mutagenic activity ranged from 193 to 8462 net revertants/mmol of creatinine, while urinary nicotine plus metabolites and cotinine levels varied from 0.007 to 1.366 and from 0.011 to 0.297 mg/mmol creatinine. Urine samples with nicotine metabolite levels of < 0.33, 0.33- < 0.66 and > 0.66 mg/mmol creatinine had mean values +/- SD of mutagenic activity of 490 +/- 222 (n = 10), 964 +/- 560 (n = 9) and 2692 +/- 2807 (n = 7) revertants/mmol of creatinine, respectively, the statistical comparison between the groups being positive (Mann-Whitney U-test, P < 0.05). The mutagenic activity of urine samples from smokers correlated well with urinary nicotine plus metabolite levels (r = 0.658, P < 0.01). A less close correlation was found between urinary mutagenic activity and other indicators of tobacco smoke exposure, such as urinary cotinine (r = 0.504, P < 0.05), number of cigarettes smoked during the day of urine collection (r = 0.399, P < 0.05) and machine smoking-derived nicotine deliveries of the total number of cigarettes smoked (number of cigarettes multiplied by the nicotine content of each cigarette, as indicated by the manufacturer; r = 0.439, P < 0.05). These results suggest that the mutagenic activity of smokers' urine may be predicted by the urinary level of nicotine plus metabolites. The low degree of reliability of many presumptive indicators of exposure to tobacco smoke and the different urinary excretion kinetics of tobacco smoke mutagens with respect to cotinine (a frequently used biomarker for monitoring exposure to tobacco smoke) are both emphasized.

Cotinine↗

PubMed1995

Mutagenicity and contents of polycyclic aromatic hydrocarbons in new high-viscosity naphthenic oils and used and recycled mineral oils.

Mutagenic activity on the Ames test was evaluated in 15 samples of naphthenic high-viscosity mineral oils and 12 samples of used lubricants (recovered and pooled) and their recycled products. Bacterial mutagenesis was assayed using both the standard technique and Blackburn's modification. The contents of polycyclic aromatic hydrocarbons (PAH) was also evaluated, as polynuclear aromatic fraction (PAF) and total PAH, determined respectively with the semi-quantitative dimethylsulphoxide-refractive index method and the Grimmer method. Only four samples (three acid-treated naphthenic oils and one recycled fraction of a used oil) showed mutagenic activity higher than 6 revertants/mg of oil, considered by Blackburn and coworkers as indicating a potential carcinogenic risk for these compounds. Limited mutagenicity was found in all used and recycled oils, but also in samples of acid- or solvent-treated oils. No hydrogen-treated naphthenic oils turned out to have any mutagenic activity. PAF contents of oils were closely correlated with those of total PAH (n = 15, r = 0.83; n = 12, r = 0.91; p < 0.01 for both naphthenic and used/recycled oils respectively). No recycled oil had high PAF contents. Eleven samples had PAF contents higher than 3%, the arbitrary danger threshold suggested by the CONCAWE (1988). Of these 11 samples, the majority were acid-treated products, although there was one hydrogen-treated oil and one used and recycled oil. No mutagenic activity could be demonstrated in almost half the oils with PAF > 3%. In this study, the presence of mutagens was not correlated wither with PAF or with total or mutagenic PAH. The difficulty of predicting the mutagenicity of mineral oils is stressed. Most naphthenic and some recycled oils clearly have components which inhibit the metabolizing system in the bacterial mutagenesis test, with consequent possible false negative results.

Biotransformation↗

PubMed1995

Urinary excretion of mutagens in coke oven workers.

The influence of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) on urinary mutagenic activity was assessed in 75 coke oven workers, using a highly sensitive bacterial mutagen technique (extraction with C18 resin and liquid micro-preincubation test on strain TA98 of Salmonella typhimurium in the presence of metabolizing and deconjugating enzymes). Exposure to PAHs was assessed according to the urinary excretion of 1-pyrenol; the main confounding factors were checked by the number of cigarettes smoked per day and the levels of nicotine and its metabolites in urine, or by ascertaining whether recommended dietary restrictions had been followed. Of the 20 urine samples which turned out to be positive (producing at least double the number of spontaneous revertants), 19 (95%) belonged to smokers. Only one non-smoker had obvious urinary mutagenic activity, and was highly exposed occupationally to PAHs (urinary 1-pyrenol of 3.930 mumol/mol of creatinine). Of the five urine samples from subjects who had not followed the recommended diet, two (40%) were clearly mutagenic. Multiple regression analysis (n = 67) showed that the presence of samples positive for urinary mutagenic activity depended only on smoking habits, if this confounding factor was assessed according to the number of cigarettes smoked per day, while the significant influence of exposure to PAH could be shown when the confounding factor was objectively estimated according to the urinary levels of nicotine and its metabolites. Assessment of the mutagenic potency of urinary extracts (net revertants/mmol creatinine) confirmed the strong influence of smoking habits on urinary mutagenic activity (all smokers 2156 +/- 2691 versus non-smokers 939 +/- 947 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). In smokers highly exposed to PAHs, greater excretion of mutagens with respect to low-exposure smokers was revealed (3548 +/- 4009 versus 1552 +/- 1227 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). Multiple regression analysis showed that the mutagenic potency of urinary extracts of coke oven workers depended on exposure to PAHs, tobacco smoking habits, and consumption of fried, grilled or barbecued meat. Increased urinary mutagenic activity strengthens epidemiological evidence of the increased risk of renal and urinary tract tumours in these workers. The presence of mutagenic metabolites in urine as a result of occupational exposure to PAH may be demonstrated only by using highly sensitive techniques for assessing urinary mutagenic activity in studies which include careful checking of the main confounding factors.

Coke↗

PubMed1994

Mutagens in indoor air particulate.

Twenty-seven extracts of airborne particulate from domestic environments, both in the absence of sources of pollution and during activities such as smoking tobacco, using a fireplace, and cooking using grills and barbecues, and eight control samples of outdoor particulate were tested using the Salmonella/microsome assay on strains TA98 and TA98NR. Dust levels and mutagenic activity in the indoor environments turned out to be very low in the absence of polluting sources, with highest mean values in winter of less than 0.1 mg/m3 and 6 and 12 revertants/m3, respectively without and with S9. The specific mutagenic activity of indoor dust ranged from 22 and 137 revertants/mg, with a contribution of nitroarene compounds of about 50%, indicating that, in city indoor air, the main cause of background particulate pollution is very probably penetration of traffic fumes from the outside. In contrast, in a country house far from traffic, very low dust and mutagenicity levels were found, without the influence of nitroarene compounds. The presence of autochthonous polluting sources, such as tobacco smoke and fumes from cooking and wood or charcoal burning, greatly increased indoor dust levels, especially during cooking operations, which reached 25.5 and 31.6 mg/m3. The particulate produced by the various indoor pollution sources showed varying specific mutagenic activities. The highest values were found for fumes produced by burning charcoal and wood, smoking tobacco, and cooking foods with high animal protein contents. Mutagens responsible were mainly direct-acting in the case of fumes from burning wood or charcoal, and required mammalian metabolic activation in the case of fumes from tobacco and meat, with a lower contribution (maximum 33%) of nitroarenes than in urban particulate.

Air↗

PubMed1993

Urinary excretion of 1-pyrenol in automotive repair workers.

The urinary excretion of a pyrene metabolite was evaluated in 65 automotive repair workers whose skin was exposed to used mineral oils, and in 41 controls. Pyrene contents were determined in oily material taken from cloths used to clean various types of engines (n = 8) and were found to vary (mean +/- SD) from 2.8 +/- 0.4 ppm for dirty matter obtained from diesel truck engines to 9.3 +/- 8.2 ppm for that from petrol car engines. Tobacco smoking and polycyclic aromatic hydrocarbon (PAH)-rich diets were considered as confounding factors. At both the beginning and the end of the working week, the values of urinary 1-pyrenol were slightly higher in exposed subjects (0.178 +/- 0.150 and 0.194 +/- 0.135 mumol/mol creatinine on Monday and Friday, respectively) than in controls (0.124 +/- 0.090 mumol/mol creatinine) (Mann-Whitney test, z = 2.741, P < 0.01). The urinary 1-pyrenol values were higher in both smoking and non-smoking subjects than in controls. The highest values were found in urinary samples of smokers exposed to used mineral oils (0.259 +/- 0.201 mumol/mol creatinine). In non-smoking workers (n = 40), post-shift 1-pyrenol values were 0.154 +/- 0.105 mumol/mol creatinine, as against 0.083 +/- 0.042 mumol/mol creatinine for the 19 non-smoking controls (Mann-Whitney test, z = 2.765, P < 0.01). In automobile repair workers, urinary 1-pyrenol values before the beginning of the weekly workshift did not differ substantially from those measured at the end of the week, not being related to the subjective degree of dirty skin as stated by workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Automobiles↗

PubMed1992

Sensitivity of different bacterial assays in detecting mutagens in urine of humans exposed to polycyclic aromatic hydrocarbons.

The urine mutagenicity and excretion of 1-hydroxypyrene (1-OH PYR) in non-smoking psoriatic patients treated topically with coal-tar-based ointments were analysed in order to find the most appropriate procedure for monitoring occupational PAH exposure. The bacterial mutagenicity assays used were the plate incorporation, macro-scale fluctuation and microsuspension tests, all on Salmonella typhimurium strain TA98 in the presence of S9 mix and beta-glucuronidase. The sensitivities of the three assays in detecting mutagenic urinary PAH metabolites were compared. The efficiencies of XAD-2 and C18 resins for concentrating PAH urinary mutagens were evaluated in the microsuspension assay. The plate and fluctuation tests on XAD-2 urine extracts were shown to be insufficiently sensitive to detect low urinary levels of mutagens, being positive on urine samples with very high PAH metabolite content, estimated as more than 30 micrograms/g of creatinine of 1-OH PYR. The microsuspension assay on XAD-2 or, even better, on C18 urine extracts was very sensitive in detecting up to 5 micrograms/g of creatinine of 1-OH PYR. It therefore seems to be applicable to the biological monitoring of most occupational low exposures to coal tar.

Coal Tar↗

PubMed1992

Micronucleated cells in nasal mucosa of formaldehyde-exposed workers.

The frequency of micronuclei (MN) and cytology of respiratory nasal mucosa cells were evaluated in 15 non-smokers exposed to formaldehyde in a plywood factory. Each subject was paired with a control matched for age and sex. Mean levels of exposure to formaldehyde ranged from about 0.1 mg/m3 in the sawmill and shearing-press departments to 0.39 mg/m3 in the warehouse area. There was a contemporary exposure to low levels of wood dust (inspirable mass ranged from 0.23 mg/m3 in the warehouse to 0.73 mg/m3 during sawing operations). Nasal respiratory cell samples were collected by an otorhinolaryngologist near the inner turbinate using a brush for endocervical cytology. After staining (Feulgen plus Fast Green and Papanicolaou's method for MN analysis and cytology, respectively), about 6000 cells were screened for micronuclei and scored in parallel for cytology according to a histopathological scale. A higher frequency of micronucleated cells was observed in the exposed group than in the controls (0.90 +/- 0.47 vs. 0.25 +/- 0.22, Mann-Whitney U test: p less than 0.01). Cytological examination indicated chronic phlogosis in the nasal respiratory mucosa of plywood factory workers, with a high frequency of squamous metaplasia cells (mean score 2.3 +/- 0.5 vs. 1.6 +/- 0.5 in the control group, Mann-Whitney U test: p less than 0.01).

Adult↗