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Biomedical subjects

G Grimmer

Publications and source records attributed to G Grimmer.

At least 19 recordsLinked to original sources
PubMed1992

DNA adduct formation in mice following treatment with used engine oil and identification of some of the major adducts by 32P-postlabelling.

Used engine oil from a petrol-powered vehicle was fractionated by column chromatography into seven parts for which the major polycyclic aromatic hydrocarbon (PAH) components were determined by GC. Topical treatment of mice with the fractions and 32P-postlabelling of the skin DNA resulted in the detection of multiple adduct spots on TLC for some, but not all, of the fractions. The majority of the DNA binding capacity of the used engine oil was possessed by the first three fractions, (equivalent to 25, 15 and 14.5%, respectively) of the adduct forming ability of the unfractionated oil. The chromatographic mobilities of the adduct spots induced by these fractions were compared to those produced by unfractionated used engine oil. In addition, mice were also treated topically with reference PAHs, either singly or as mixtures, dissolved in unused oil at the concentrations at which they were present in the used oil. Comparisons were made between the chromatographic mobilities of the adducts formed in mouse skin DNA by synthetic mixtures with those formed by the used oil. From these data, some of the major adducts produced by treatment with used engine oil are suggested to be formed by reactive metabolites of benzo[b]naphtho[1,2-d]thiophene, benzo[c]phenanthrene, benzo[g,h,i]fluoranthene, chrysene, benzo[a]pyrene and benzo[g,h,i]perylene.

Animals↗
PubMed1991

Rat liver microsomal ring- and S-oxidation of thiaarenes with central or peripheral thiophene rings.

The metabolism of the following thiaarenes has been investigated using liver microsomes of untreated, phenobarbital-, AroclorR- and 5,6-benzoflavone-pretreated rats: dibenzothiophene, naphtho[2,1-b]thiophene, benzo[b]naphtho[2,1-b]thiophene, benzo[b]naphtho[1,2-d]thiophene, benzo[b]naphtho-[2,3-d] thiophene, phenanthrol[1,2-b]thiophene, phenanthrol[4,5-bcd] thiophene, triphenyleno[1,12-bcd]-thiophene and dinaphtho[2,1-b:1',2'-d]thiophene. Thiaarenes with a central thiophene ring preferentially undergo S-oxidation and are converted into sulfoxides and sulfones, whereas those with a peripheral thiophene ring are oxidized at the carbocyclic skeleton resulting in the formation of phenols, dihydrodiols and triols. Sulfone formation seems to be inducible by phenobarbital but only little or not by 5,6-benzoflavone treatment. In most cases 5,6-benzoflavone and AroclorR treatment enhanced the rates of ring oxidation.

Animals↗
PubMed1990

Evaluation of the carcinogenic potency of 4 environmental polycyclic aromatic compounds following intrapulmonary application in rats.

The carcinogenic potential of 4 highly purified polycyclic aromatic compounds (PAC) was studied in the respiratory tract of rats. Using a beeswax/trioctanoin mixture as vehicle, 10, 3 and 1 mg phenanthrene (PHE), 3 and 1 mg chrysene (CHR), 0.1 mg dibenz(a,h)anthracene (DBahA) and 6, 3 and 1 mg benzo(b)naphto(2,1-d)thiophene (BNT) were injected into the lungs of 35 female Osborne-Mendel rats per group. Benzo(a)pyrene (BaP, 0.3, 0.1 and 0.03 mg) was used as the reference substance. Whereas only one squamous cell carcinoma developed at the highest PHE dose, a dose-dependent tumor incidence was found for CHR. BNT showed a carcinogenic effect similar to CHR, but an increasing incidence of neoplasms was not seen between the median and high dose. DBahA induced carcinomas in even more than half of the animals at the dose level of 0.1 mg and, therefore, has to be classified as the most potent PAC under investigation. BaP resulted in a clear dose-response relationship. According to probit analysis of the results, the carcinogenic potencies of the PAC relative to BaP (1.00) rank as follows: DBahA, 1.91; CHR, 0.03; BNT, 0.02; and PHE, 0.001. The estimated ED10- values were 0.031 mg for BaP, 0.016 mg for DBahA, 1.02 mg for CHR, 1.65 mg for BNT and 22.84 mg for PHE.

Animals↗
PubMed1990

Analysis of the polycyclic aromatic hydrocarbon content of petrol and diesel engine lubricating oils and determination of DNA adducts in topically treated mice by 32P-postlabelling.

Engine lubricating oils are known to accumulate carcinogenic polycyclic aromatic hydrocarbons (PAHs) during engine running. Oils from nine petrol-powered and 11 diesel-powered vehicles, in addition to samples of unused oil, were analysed for PAH content and ability to form DNA adducts when applied topically to mouse skin. The levels of 19 PAHs, determined by GC, were in total, approximately 22 times higher in used oils from petrol engines than in oils from diesel engines. Male Parkes mice were treated with 50 microliters of oil daily for 4 days before they were killed and DNA isolated from skin and lung tissue. DNA samples were analysed by nuclease P1-enhanced 32P-postlabelling. Used oils from both diesel and petrol engines showed several adduct spots on PEI-cellulose plates at total adduct levels of up to 0.57 fmol/microgram DNA [approximately 60 times greater than in experiments with samples of unused oil in which adduct levels (0.01-0.02 fmol adducts/microgram DNA) were close to the limit of detection]. Higher adduct levels were generally formed by petrol engine oils than by diesel engine oils. Lung DNA contained similar total adduct levels to those in skin although the adduct maps were less complex. Total adduct levels correlated with extent of oil use in the engine, the total PAH concentration in oils and with the concentrations of certain individual PAHs present in the oils. An adduct spot that co-eluted with that of the major benzo[a]pyrene-DNA adduct accounted for 9-26% of the total adducts in skin DNA, and approximately 8% of the adducts in lung DNA, of mice treated with petrol engine oils. A major, and as yet unidentified, adduct spot comprised up to 30% of the total adducts in skin DNA, and up to 89% of the total adducts in lung DNA, of these animals.

Administration, Topical↗
PubMed1990

Dietary influences on urinary excretion of hydroxyphenanthrenes, thioethers and mutagenicity in man.

Our study indicates that large differences in dietary polycyclic aromatic hydrocarbon (PAH) content in humans are not reflected by urinary and faecal excretion of hydroxyphenanthrenes, although significant increases in 3-hydroxybenzo[a]pyrene and 3-hydroxychrysene in faeces were observed after consumption of a diet rich in PAHs. The question therefore arises whether urinary hydroxyphenanthrenes are a reliable marker for exposure to PAHs. As expected, the elevated mutagenicity of the diet rich in PAHs led to increased mutagenic activity in urine. The increased urinary excretion of thioethers after this diet was probably due to its higher thioether content. Therefore, an elevated thioether excretion does not always indicate exposure to electrophilic compounds.

Adult↗
PubMed1986

The predominant role of S-oxidation in rat liver metabolism of thiaarenes.

Thiaarenes are metabolized by liver microsomes of untreated rats predominantly to sulfones and sulfoxides. After pretreatment of rats with monooxygenase inducers, ring oxidation of thiaarenes is also observed. In case of benzo[b]naphtho[2,3-d]thiophene the formation of a p-quinone takes place. Rat liver microsomal metabolism of the thiaarenes tested as substrates did not resemble that of the polycyclic aromatic hydrocarbon (PAH) isosters at all.

Animals↗
PubMed1985

Determination of mutagenic activities in different fractions of automobile exhaust condensate by the Salmonella/oxygenase mutagenicity test system.

Automobile exhaust condensate of a passenger car (gasoline engine) was separated into fractions of 2-3 rings containing -, 4-7 rings containing polycyclic aromatic hydrocarbons (PAHs) and PAH-free fractions. All fractions were tested for mutagenicity by the Ames system. The highest dose-dependent increase in revertant colonies was found for the 4-7 ring PAH-fraction when tested with Salmonella typhimurium TA 98 and TA 100. These results are compatible with data obtained in in-vivo tests by previous investigations. The mutagenicity of these fractions in the absence of the oxygenase was negligible.

Animals↗
PubMed1979

[Profiles of polycyclic aromatic hydrocarbon metabolites after treatment with various inducers of microsomal rat liver monoxygenases (author's transl)].

The microsomal oxidation of 12 frequently occurring environmental polycyclic aromatic hydrocarbons after incubation with rat-liver microsomes has been studied and their metabolites characterized by means of gas-liquid chromatography/mass spectrometry. The method enables the detection and characterisation of phenols, diols, triols, and tetrols as trimethylsilyl ethers beside the original hydrocarbons. Moreover, the induction properties of some carcinogenic and non-carcinogenic hydrocarbons (benz[a]anthracene, pyrene, chrysene, benzo[a]-pyrene, benzo[e]pyrene, benzo[b]fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene) have been studied. Except pyrene and benzo[e]pyrene, all compounds investigated significant but different induction factors. The relevance of the induction for an estimation of the biological effect of environmental polycyclic aromatic hydrocarbons is discussed.

Animals↗
PubMed1977

Analysis of automobile exhaust condensates.

1. On the basis of figures for the production of PAH during the Europa drive cycle by 100 passenger cars and those for the consumption of petrol in the Federal Republic of Germany, an annual emission of 1,850 kg benzo[a]pyrene from petrol engine vehicles has been calculated. 2. The carcinogenic effect of benzo[a]pyrene accounts for only 9% of the total activity of exhaust condensates. 3. The amounts of other known carcinogenic PAH, such as benzo[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[j]fluoranthene, indeno[1,2,3-cd]pyrene and dibenzo[a,h]anthracene are shown in Table 2. (table: see text). Assuming that there is no significant promoting or hyper-additive effect, it can be estimated that these six known carcinogenic PAH contribute about 10-15% of the total carcinogenicity. 4. Six unknown PAH were found: cyclopenteno[cd]pyrene (mol wt 226), methylenebenzo[a]pyrene (mol 264), methylenebenzo[e]pyrene (mol wt 264), methylenebenzo[ghi]perylene (mol wt 288), PAH mol wt 300A and PAH mol wt 300B. It is reasonable to assume that these unknown PAH account for the predominant part of the carcinogenic effect. Biological tests with these pure substances are being undertaken by Drs Pott, Pfeiffer and Habs. 5. It has been shown that almost all of the carcinogenic effect of automobile exhaust condensates is due to PAH. To support this claim, the carcinogenic effects of the exhaust condensate should be compared with those of a mixture of the known and unknwon PAH in the same proportions as are found in the exhaust condensate. The gas chromatogram of such a mixture is shown in Figure 6.

Benzopyrenes↗
PubMed1977

Investigation on the carcinogen burden by air pollution in man. XV. Polycyclic aromatic hydrocarbons in automobile exhaust gas--an inventory.

Polycyclic aromatic hydrocarbons (=PAH) emitted by two different vehicles were separated by gas chromatography and characterized by mass spectrometry after enrichment from exhaust gas condensate. Gasoline was investigated also using this technique. The quantities of PAH with boiling points higher than 338 degrees C contained in the exhaust gas were compared to those present in the fuel. About 150 different PAH have been characterized by mass spectrometry, 75 of these were identified by means of comparison with authentic samples. Six compounds of the PAH-group consisting of 4-7 rings, which are suspected of possessing carcinogenic activity, are described here for the first time. Structures of these hitherto unidentified PAH are proposed by means of MS and UV spectral informations (11H-cyclopenta(qrs)benzo(e)-pyrene, 10H-cyclopenta(mno)benzo(a)pyrene, benzo(ghi)cyclopenta(pqr)perylene, cyclopentenopyrene). According to the different PAH-profiles of the fuel and of the exhaust gas, it is concluded that the main part of the PAH emitted is produced de novo during the combustion in the engine and furthermore that the PAH contained in the fuel are combusted for the most part.

Carcinogens↗
PubMed1976

Investigations on the carcinogenic burden by air pollution in man. XIV. Effects of automobile exhaust condensate on the Syrian golden hamster lung.

Syrian golden hamsters were intratracheally instilled with 5 or 2.5 mg/animal of automobile exhaust condensate at two weekly intervals. Moribund animals were fixed by intravascular perfusion. Samples of lobar and segmental bronchi, as well as of peripheral lung tissue, were taken for electron microscopical examination. In addition, all organs were examined histologically. After a survival time of 30 to 60 weeks all animals developed multiple pulmonary adenomas, thus indicating a marked carcinogenic effect of automobile exhaust condensate.

Adenoma↗
PubMed1975

Profile analysis of polycyclic aromatic hydrocarbons and metal content in sediment layers of a lake.

The question is investigated whether polycyclic aromatic hydrocarbons (PAH) in the annual sediment layers of a lake mainly result from air dust pollution. Sample layers taken from drilling cores going back to 1915 show no significant differences at the forest shore (no buildings) during this period. In contrast, samples taken from a built-up area of the shore (with a highway and a main railway line) show today 5 times the amount of PAH compared with 1915. The same trend is observed in the content of Zn, whereas Pb, Fe, Cr, Ni, Cu and Mn levels are constant. Identification or characterization of PAH was accomplished by comparison of the retention times and mass spectrometry of authentic compounds. Sixty-four PAH are described. The results indicate that the burden of carcinogenic PAH air pollutants has increased 5-fold from 1915-1970.

Air Pollutants↗
PubMed1975

Polycyclic aromatic hydrocarbon profile analysis of high-protein foods, oils, and fats by gas chromatography.

A method is described for the determination of polycyclic aromatic hydrocarbons (PAHs) with 3-7 rings in (I) meat, poultry, fish, and yeast; and (II) oils and fats. The extraction of PAHs from group I is incomplete, and, therefore, group I samples must be dissolved homogeneously by saponification in 2N methanolic potassium hydroxide. The PAHs are concentrated by liquid-liquid extraction (methanol-water-cyclohexane, N,N - dimethylformamide - water-cyclohexane) and by column chromatography on Sephadex LH 20. The PAHs are separated by high-performance gas-liquid chromatography (GLC) with columns containing 5% OV-101 on Gas-Chrom Q and estimated by integration of the flame ionization detector signals in relation to an internal standard (3,6-dimethylphenanthrene and/or benzo(b)chrysene). The sensitivity is significantly higher than that obtained with ultraviolet spectroscopic methods. The reproducibility and margin of error were tested with meat samples fortified with 11 PAHs and with samples of sunflower oil. The method was further applied to meat, smoked fish, yeast, and unrefined sunflower oil. All samples investigated contained more than 100 PAHs (characterized by mass spectrometry) of which only the main components were determined: phenanthrene, anthracene, fluorene, fluoranthene, pyrene, benzo(a)anthracene, chrysene, benzo(b)fluoranthene + benzo (j)fluoranthene + benzo(k) fluoranthene, benzo(e)pyrene, benzo(a)pyrene, perylene, dibenz(a,j)anthracene, dibenz(a,h)anthracene + indeno(1,2,3,-cd)pyrene, benzo(ghi)perylene, anthanthrene, and coronene. In contrast to other methods, the GLC profile analysis allows the recording of known and unknown PAH peaks simultaneously and also allows a compilation of all PAHs.

Chromatography, Gas↗