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Biomedical subjects

R Puntoni

Publications and source records attributed to R Puntoni.

At least 37 records · Page 2Linked to original sources

32P-postlabeling detection of aromatic adducts in the white blood cell DNA of nonsmoking police officers.

Atmosphere in urban areas may be polluted by a number of combustion sources, including industries, vehicle traffic, and residential heating. Traffic police constitute a group of workers that is highly exposed to urban pollutants, especially those from motor vehicle exhaust. We conducted a biomonitoring study to simultaneously measure in 34 nonsmoking police officers and in 36 nonsmoking office workers, as referents, the individual benzo(a)pyrene [B(a)P] exposure using personal samplers and the formation of DNA adducts in peripheral WBCs using 32P-postlabeling techniques. Our results show that the police officers were exposed to significantly higher levels of B(a)P than were referents (P < 0.0001). No seasonal variation of the atmospheric levels of B(a)P was found throughout the year. The median relative adduct labeling x 10(-8) values of the controls and exposed police officers were 0.94 (range, 0.1-3.7) and 1.3 (range, 0.1-5.5), respectively, using the nuclease P1 technique. Although the DNA adduct levels of police officers were globally higher than those of referents (P < 0.05), the difference was entirely due to the summer difference [median values 0.80 (range, 0.1-1.8) and 2.8 (range, 0.7-5.5), respectively (P < 0.001)]. In winter, the DNA adduct levels were substantially identical, and in midseason, there was only a very small increase in police officers, with respect to controls (statistically not significant). Moreover, a more significant seasonal variation of bulky aromatic DNA adduct levels was observed in WBC DNA samples of police officers (P < 0.05) compared to those of referents. The seasonal variation of bulky aromatic adduct levels could be correlated with the reported seasonal variation of aryl hydrocarbon hydroxylase inducibility in human lymphocytes.

Adult↗

Urinary excretion of 1-hydroxypyrene as a marker for exposure to urban air levels of polycyclic aromatic hydrocarbons.

A cross-sectional study was conducted among 94 traffic police officers from the Municipality Police of Genoa, Italy, exposed to airborne pollutants and 52 referent subjects exposed to indoor air pollution levels to investigate the relationships between exposure to ambient air polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene (1-OH-P). The effects of smoking, lifestyle factors such as exposure to ETS, and diet, along with the role played by the cytochrome P4501A1 (CYP1A1), and glutathione S-transferase M1 and theta metabolic susceptibility gene polymorphisms were examined. The geometric mean of benzo(a)pyrene air measurements (an index compound of PAH levels) was 70 times higher in traffic police officers (3.67 ng/m3) than in referents (0.05 ng/m3). The urinary concentration of 1-OH-P was clearly associated with cigarette smoking and, to a lesser extent, with exposure to ETS and particulate PAH pollution. No association was detected between 1-OH-P excretion and diet. Women exhibited a higher excretion level than did men, and an apparent effect of age was due to differences in cigarette smoking habits. Exposure to PAHs resulted in higher levels of 1-OH-P excretion in all groups except heavy smokers. Overall, no significant role of any metabolic polymorphism was detected. However, stratification of study subjects according to their smoking habits revealed higher levels of excretion of 1-OH-P in subjects smoking < or =15 cigarettes/day carrying the CYP1A1 polymorphism. No such effect was seen either with nonsmokers or with people smoking more than 15 cigarettes/day. These findings are suggestive of a gene-environment interaction, in which subjects with the CYP1A1 polymorphism, relative to subjects without it, have higher levels of 1-OH-P in their urine at low doses of exposure to PAHs.

Age Distribution↗

Presence and persistence of serum anti-benzo[a]pyrene diolepoxide-DNA adduct antibodies in smokers: effects of smoking reduction and cessation.

Among biomarkers of tobacco smoke (TS)-induced genotoxic damage, benzo[a]pyrene diolepoxide-DNA adducts (BPDE-DNA) are extensively studied. Adducted DNA becomes antigenic and antibodies anti-BPDE-DNA (BPDE-DNA-Abs) may be found in serum of exposed subjects. Little is known about the persistence of BPDE-DNA, and no study has been performed to evaluate the persistence of BPDE-DNA-Abs after cessation of exposure. Fifty heavy smokers, enrolled in a smoking cessation program with nicotine patch substitution therapy, were evaluated for the presence of BPDE-DNA-Abs before (w0) and 1, 3, 6 and 12 weeks (w1-12) after the start of the program. Nicotine or placebo patches were randomly assigned to the subjects. BPDE-DNA-Abs were determined in serum by non-competitive ELISA. After the start of the cessation program, 28 subjects quit smoking (group Q) and the other 22 reduced by about 75% the number of cigarettes smoked per day (group R). At the start of the program (w0) 8% of subjects were positive. At w1 the prevalence of positivity had increased both in subjects who quit smoking (Q: 21%) and in subjects who had reduced the number of cigarettes per day (R: 27%). Positivity remained stable up to w12 (21%) for group Q, whereas it increased to 41% in group R. Serum BPDE-DNA-Abs can be detected in smokers, and their persistence for months after smoking cessation suggests their usefulness for relatively long-term surveys. The low percentage of positivity in actual heavy smokers and the increase in antibody positivity with smoking cessation or reduction must be taken into account when interpreting serum BPDE-DNA-Ab measurement in exposed individuals.

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

Chromosome aberrations in hospital workers: evidence from surveillance studies in Italy (1963-1993).

Hospital workers are occupationally exposed to various agents known or suspected to induce chromosome damage, the most studied being ionizing radiation. To determine the extent of chromosome damage in peripheral blood lymphocytes in this population, taking into account temporal changes and job titles, a re-analysis of cytogenetic studies performed in four Italian laboratories in the period 1965-1993 was carried out. A total of 871 hospital workers and 617 controls, mainly coming from ad hoc studies or surveillance programs in occupational groups potentially exposed to ionizing radiation, were examined. The exposed to controls frequency ratio of chromosome aberrations was evaluated as the measure of effect within each dataset by job title, using multivariate Poisson regression analysis, which allowed an efficient control of confounding. Increased frequency of chromosome-type aberrations among exposed subjects was found in all datasets, especially in those dealing with older data. Significantly higher frequencies are reported for various job titles, particularly for orthopedists, radiologists, anesthesists, and nurses among paramedical occupations. Decrease in exposure to ionizing radiation in hospital workers was documented through a targeted study in the critical group of radiologists. A similar time-related reduction in the frequency of chromosome-type aberrations also has been reported by the surveillance studies carried out over the most recent decades. These data substantiate the use of chromosome-type aberrations as biomarkers of exposure in this occupational setting in the period evaluated. However, the increases observed also in workers with doubtful exposure to ionizing radiation indicate that other chromosome-damaging agents may be involved and, in turn, suggest the extension of surveillance to a larger number of occupations.

Adult↗

Mortality in a cohort of tannery workers.

OBJECTIVES: To evaluate the mortality of a group of tannery workers. METHODS: The cohort consisted of 1244 workers (870 men and 374 women) employed at a chrome tannery between 1955 and 1988. A total of 36414 person-years of follow up was calculated (369 people had died). National and regional mortalities were used to estimate the expected numbers. RESULTS: All cause mortality was similar to that of the general population. The most remarkable excess was for bladder cancer (observed 10, standardised mortality ratio (SMR) 242, 95% confidence interval (95% CI) 116 to 446). An excess of colorectal cancer (observed 17, SMR 180, 95% CI 105 to 288) was also found, based on an increased risk of both colon (SMR 166) and rectal cancer (SMR 206). No recognisable patterns emerged from the analyses by years since first employment, calendar year of hire, or lagging exposures. CONCLUSIONS: The increased mortality from bladder cancer is likely due to exposure to benzidine based leather dyes. If the apparent excess of colorectal cancer is real, its causes are as yet unknown.

Adolescent↗

Plasma 3-nitrotyrosine in cigarette smokers.

Peroxynitrite has been associated with increased oxidative reactions and DNA damage in inflamed tissues as it may cause a reduction of plasma antioxidants as well. Nitration of tyrosine residues of proteins leads to the production of 3-nitrotyrosine (NTYR), which may be considered as a marker of NO.-dependent oxidative damage. We developed a highly sensitive method to detect NTYR in human plasma and tested it in cigarette smokers and in healthy control subjects. Peripheral venous blood (10 ml) was obtained in 20 healthy, asymptomatic cigarette smokers (13 males, 7 females; age: 49 +/- 11 yr) and in 18 healthy nonsmokers (10 males and 8 females; age: 36 +/- 6 yr). In smokers, plasma nicotine, cotinine, and expired CO levels were measured. NTYR was determined with a sequential HPLC/gas chromatography-thermal energy analysis (GC-TEA) technique. The total plasma Trolox-equivalent antioxidant capacity (TEAC) was also measured using metmyoglobin as peroxidase and a phenothiazine as a radical donor. NTYR was detectable (detection limit: 0.02 ng/injection) in 11 smokers (mean +/- SD: 1.60 +/- 1.24 ng/mg protein) and in two nonsmokers (1.10 and 1.20 ng/mg protein, respectively). NTYR was not associated with nicotine and cotinine levels or expired CO in smokers. Plasma TEAC in smokers was significantly lower (0.43 +/- 0.38 mM) than in nonsmokers (1.42 +/- 0.3 mM; p < 0.001) and showed a biphasic, negative relationship with NTYR (r = 0.96, p < 0.001). This highly sensitive HPLC/GC-TEA method for detection and quantitation of plasma NTYR may be used for monitoring oxidative reactions associated with tobacco smoking. This assay might be incorporated into molecular epidemiologic studies for lung chronic inflammatory and neoplastic disorders in which exposure to oxidants may be an important risk factor.

Adult↗

Age-related increase of baseline frequencies of sister chromatid exchanges, chromosome aberrations, and micronuclei in human lymphocytes.

Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter- and intralaboratory variability. A greater frequency of the mean standardized values by increasing of age was observed for all of the end points. A leveling off was evident in the last age classes in the trend of MN frequencies. Frequency ratios (FRs), which express the increase of the cytogenetic damage with respect to the first age classes, i.e., 1-19 years, were estimated using Poisson regression analysis after adjustment for the potential confounding factors and confirmed the increasing trend by age class for all three end points. The most dramatic increase was observed for MN, with a FR that approaches the value of 2 at the age class 50-59 (FR, 1.97; 95% confidence interval, 1.43-2.71) and remains substantially unchanged thereafter. The trend of FRs for CA is more homogeneous, with a constant rise even in the older classes, whereas the frequency of SCE increases with age to a lesser extent, reaching a plateau in the age class 40-49 and the maximum value of FR in the age class over 70 (FR, 1.14; 95% confidence interval, 1.07-1.23). In conclusion, our results point to an age-related increase of the chromosome damage in lymphocytes and emphasize the need to take into account the potential confounding effect of this variable in the design of biomonitoring studies based on chromosome damage.

Adolescent↗

Airborne levels of polycyclic aromatic hydrocarbons: 32P-postlabeling DNA adducts and micronuclei in white blood cells from traffic police workers and urban residents.

An epidemiologic study on 94 traffic police officers exposed to airborne polycyclic aromatic hydrocarbons (PAH) and 52 age-matched urban residents working in confined spaces considered as referent subjects without occupational exposure to PAH was conducted to characterize individual exposure to benzo(a)pyrene (BaP), benzo(b)-, and benzo(k)fluoranthene (BbF and BkF) and the occurrence of DNA adducts and micronuclei in white blood cells (WBC). The study's findings indicated that mean concentrations of PAH in the city air were 10 to 30 times higher among the traffic police officers compared with referent subjects (4.55 +/- 3.44 ng/m3 and 0.15 +/- 0.30 ng/m3 of BaP among police officers and referents, respectively). 32P-postlabeling DNA adducts in WBC obtained from police officers (1.48 +/- 1.35 RAL/10(8)) were significantly higher than in referent subjects (1.01 +/- 0.63 RAL/10(8), P = 0.007), suggesting a possible role of exposure to airborne PAH in the DNA damage. The frequency of micronuclei was significantly increased (P = 0.02) in referent subjects (4.49 +/- 2.0% cells) compared with police officers (3.75 +/- 1.65% cells) due to the large proportion of females in the former group. Comparison of the mean micronuclei frequencies among 82 male police officers (3.73 +/- 1.6% cells) and referents (4.03 +/- 1.61% cells) failed to reveal a statistically significant difference (P = 0.38). Our findings support the evidence of a noxious effect of the exposure to airborne PAH found in large cities on the occurrence of DNA adducts in WBC, whereas there seems to be no effect on the cytogenetic risk assessed as micronuclei frequency.

Adult↗

Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch.

Nicotine replacement by transdermal patches is more effective than placebo in smoking cessation, but has a low success rate after one year (9-18%). We tested whether this was attributed to insufficient nicotine replacement. We conducted a randomized trial to investigate the effect on outcome of different doses of transdermal nicotine replacement after stratification according to baseline plasma cotinine values. Two hundred and ninety seven adult smokers were enrolled. Those with baseline cotinine < or = 250 ng.ml-1 (low cotinine) were randomly assigned to placebo (LC-P) or to 15 mg 16 h nicotine patches (LC-15), and those with baseline cotinine > 250 ng.mL-1 (high cotinine) were randomly assigned to 15 mg (HC-15) or 25 mg (HC-25) 16 h nicotine patches. Plasma nicotine and cotinine values, expired carbon monoxide and withdrawal symptoms were measured at scheduled intervals during treatment. Smokers in the LC-15 group had a significantly higher success rate than placebo (28 vs 9%). Smokers with high baseline cotinine had lower success rates, and a high dose of nicotine did not increase success rate (HC-25 9% vs HC-15 11%). Subjects in the HC-15 group had the lowest percentage of nicotine replacement and a higher prevalence of withdrawal symptoms than the HC-25 group. Replacement was similar in groups LC-15 and HC-25, but the success rate was significantly lower in HC-25 group, despite similar levels of withdrawal symptoms. We conclude that a higher success rate was obtained after one year in smokers with low baseline plasma cotinine values. Determination of plasma cotinine values may be, thus, helpful in identifying smokers who could benefit from transdermal nicotine replacement.

Adult↗

(32)P-postlabeling detection of DNA adducts in peripheral white blood cells of greenhouse floriculturists from western Liguria, Italy.

Pesticides are widely used in agriculture to enhance crop yields and to control disease vectors. Floriculturists work frequently in greenhouses and may be exposed to high levels of pesticides, which may result in adverse health effects. To evaluate the relationship between exposure to pesticides and DNA adduct formation in peripheral WBCs of Italian floriculturists, the nuclease P1 modification of a (32)P-postlabeling assay was used to analyze WBC DNA from floriculturists (n = 26) and matched controls (n = 22). DNA adduct-positive samples were more frequent in floriculturists (11/26; 42%) than in matched controls (2/22; 9%) (P < 0.01). Slightly higher frequencies of DNA adduct-positive samples were observed in floriculturists > or = 44 years of age (53%) and in female floriculturists (57%). Floricultural practice was found to be associated with a significantly higher DNA adduct-positive rate in WBCs (rate ratio, 5.12; 95% confidence interval, 1.1-23.7) after allowing for the effects of age and gender. These two latter covariates were not significantly associated with DNA adduct-positive rates. The quantitative levels of DNA adducts were significantly higher in floriculturists than in matched controls according to the Mann-Whitney nonparametric statistic (P = 0.0052). The median adduct level for positive samples among floriculturists was 1.5/10(8) bases. A specific, well-visible spot, named alpha adduct, was detected in 7 out of the 11 DNA adduct-positive samples from floriculturists but in none of the (22 + 20) referent samples (P = 0.0004). The presence of pesticide-related DNA adducts was confirmed clearly using the butanol extraction procedure. Six of 8 floriculturists and 0 of 10 referents were found positive with this method. The median adduct level for positive samples was 6.0/10(8) bases. Two strong spots close to the origin could be identified in all six positive floriculturists, using the butanol extraction procedure. No association between DNA adducts and use of specific pesticides was observed.

Adult↗

The mortality rate of the province of birth as a risk indicator for lung and stomach cancer mortality among Genoa residents born in other Italian provinces.

This study analyses the relationship between migration and mortality for lung and stomach cancer, these diseases being those considered susceptible to changes in environmental conditions and individual habits that usually follow migration. Mortality rate of the province of birth was used as the index of risk related to migration. Data were analysed using the Poisson regression model for grouped data. Results indicate that migration determines modifications in the mortality rates of the migrant populations for the diseases under study. For lung cancer, the analysis showed a greater risk for migrants originating from areas with high rates and that migrants had a reduced risk in comparison with natives of Genoa. With regard to stomach cancer, the study revealed that migrants originating from high risk areas had higher relative risks than the Genoa natives, even if these were lower than expected when compared to the risks of the populations in the regions from which the migrants originated.

Emigration and Immigration↗

Mathematical modelling in risk/exposure assessment of tobacco related lung cancer.

The existence of a dose-related increase of lung cancer risk in cigarette smokers has been indisputably established. This finding, however, is not confirmed at low doses (< 5 cigarettes/day), there still being a lack of epidemiological data. The use of mathematical models of carcinogenesis to extrapolate from higher doses allows estimation of the risk for very light smokers. The present study has been designed to compare a set of mathematical models, i.e. one-hit, two-stage, multi-stage, logit, probit, and Weibull, in extrapolating relative risks at low doses from the data of nine large cohort studies on cigarette smokers reported in the IARC Scientific Monograph on tobacco smoking. All models evaluated, apart from the one-hit, achieved a good fit, with the proportion of explained variance ranging between 61% and 67%. The relative risk estimates for passive smokers from the most updated epidemiological studies were taken into account to evaluate, on the basis of these models, the corresponding exposure in terms of 'cigarette equivalent' smoked. These values ranged from 0.21 to 0.43 cigarettes/day for the two-stage and multi-stage model, while probit, logit and Weibull models, yielded estimates one or even two orders of magnitude lower. The authors emphasize the substantial agreement between the estimates of 'cigarette equivalent' based on the application of two-stage and multi-stage models to the epidemiological evidence on the effect of passive smoking and to the data based on the comparison of tobacco metabolites in active and passive smokers.

Dose-Response Relationship, Drug↗

Cancer Incidence and Mortality in the Elderly: Profile of the Italian Problem.

In Italy, 28% of all deaths are due to cancer. Of the 15% of the population that is 65 years or older, 65% of cancer deaths occur in men and 69.5% in women. The proportional mortality and incidence of cancer in Italy varies with increasing age. All patients over 65 years are found to be at increased risk for intestinal cancers. In older men, the proportion of lung and urinary tract cancers decreases, while prostate, intestinal and gastric cancers increases. Prostate cancer predominates in men over 85 years and intestinal and gastric cancers are relatively more common than lung cancer. In women over age 74, intestinal cancer is most common. Breast, genital and lung cancers decrease rapidly with age, while stomach, liver, gallbladder and pancreatic cancers increase with age. The ratio of incidence to mortality for all cancers studied is shown to equalize with increased age, the probable result of lower hospitalization rates and less adequate cancer therapy for the elderly.

Journal Article↗

[Genotoxic damage in subjects exposed to automobile exhaust: preliminary results].

The associations between selected biomarkers of biologically effective dose (32P-post-labelling-DNA adducts), early biological effects (Micronuclei, MN) and sister chromatid exchanges (SCE) and individual measurements of exposure to benzo(a)pyrene (a surrogate index of exposure to polynuclear aromatic hydrocarbons, PAHs) are investigated in a study being conducted among traffic police workers and referent subjects in the City of Genova, Italy. Preliminary findings show B(a)P mean values of 1.33 ng/m3, SD = 1.35 ng/m3 and 0.06, SD = 0.17 in traffic police workers and referent subjects, respectively. Micronuclei mean levels in peripheral blood lymphocytes of 26 traffic police workers and 25 referents were 3.30, DS = 1.24 e 3.90, DS = 1.50 (per 1,000 binucleated cells). Eleven subjects (61%) out of 18 had detectable levels of DNA adducts (32P-post-labelling technique, range 1.8-9.0 Relative Adduct Level (RAL) per 10(9) nucleotides).

Adult↗

A case-control study of cancers of the gastric cardia in Italy.

In a case-control study of gastric cancer (GC) in high-risk and low-risk areas in Italy, 923 GCs were reviewed by one pathologist and classified according to anatomic site. There were 68 (7.4%) cancers occurring in the gastric cardia. Compared to other GCs, cardia cancer tended to occur more often in males (sex ratio 2.8 vs 1.7) and as intestinal or unclassified histologic types. Nutritional factors for cardia tumours resembled those of other GCs, showing inverse associations with the consumption of raw vegetables, citrus and other fresh fruit, and ascorbic acid, and positive associations with the intake of traditional soups and meat, protein and cholesterol, and preference for salty foods. Cigarette smoking and wine consumption were unrelated to cardia cancer risk, and there was only a weak association with total alcohol intake. Cardia tumours showed a greater familial occurrence of GC than did other sites, with a 7-fold increase in risk for those reporting two first-degree relatives with GC. The authors discuss these findings in view of the rising incidence of adenocarcinomas of the cardia and lower oesophagus that has been reported in some western countries.

Adult↗

Lung cancer risk among refractory brick workers exposed to crystalline silica: a retrospective cohort study.

We conducted a retrospective cohort study among 1,022 refractory brick workers exposed to crystalline silica. Mortality from lung cancer (SMR = 1.77) and respiratory diseases (SMR = 3.15) was elevated in workers first employed less than or equal to 1957 who are likely to have shared the highest exposure to crystalline silica. Workers with at least 19 years of cumulative employment in the plant experienced particularly increased risks for lung cancer (SMR = 2.01) and respiratory diseases (SMR = 3.89). Relative mortality from these specific causes increased with years since first employment (that is, first exposure) and decreased with age at first employment. Indirect adjustment for smoking habits and the lack of excess mortality from cardiovascular diseases and emphysema indicated little effect of smoking on the increased risks for lung cancer and respiratory diseases.

Adult↗