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PubMed2001

Changes in lipids and sterols during composting.

Pyrolysis-gas (Py-GC) chromatography was used to characterize organic [(diethyl ether (DEE) and chloroform (CHCl3)] extracts of raw and composted duck excreta enriched wood shavings from two finishing cycles (C1 and C2). Materials were collected on days 0, 8 and 23. C1 contained 1.7 % total N while C2 contained 0.9 % total N. Py-GC-MS (mass spectrometry) showed that the extracts contained n-alkanes (C12 to C32), alkenes (C12:1 to C33:1), n-fatty acids (C12 to C28), unsaturated fatty acids (C18:1 and C18:2), and sterols (cholestene, cholestadiene, stigmastene, stigmastadiene, stigmastatriene, cholesterol, stigmastanol, stigmastanone, stigmastadienone, 17-methyl dialkylsulfanyl decahydro-1H-cyclopenta [a] phenanthrene, 17-methyl dialkylsulfanyl dodecahydro-1H-cyclopenta [a] phenanthrene, and 17-methyl-17-dialkylsulfanyl decahydro-1H-cyclopenta [a] phenanthrene). Other components identified were prystene, squalene (precursor of cholesterol), phthalic acid, diphenylpropane, diphenylbut-2-ene and 1,3,6 triphenyl hex-4-ene. Our data showed significant changes in the lipid composition of duck excreta enriched wood shavings during composting, which appeared to be related to the total N content of the system.

Animals↗

PubMed2003

Extractable soil lipids and microbial activity as affected by Bt and non Bt maize grown on a silty clay loam soil.

Pyrolysis-gas (Py-GC) chromatography was used to characterize extractable lipids from Bt and non-Bt maize shoots and soils collected at time of harvesting. Py-GC-MS (mass spectrometry) showed that the concentrations of total alkenes identified in non-Bt shoots and soils were 47.9 and 21.3% higher than in Bt maize shoots and soils, respectively. N-alkanes identified were of similar orders of magnitude in Bt and non-Bt maize shoots, but were 28.6% higher in Bt than in non-Bt soils. Bt maize shoots contained 29.7% more n-fatty acids than non-Bt maize shoots, whereas the concentrations of n-fatty acids in Bt soils were twice as high as those in non-Bt soils. Concentrations of unsaturated fatty acids in Bt maize shoots were 22.1% higher than those in non-Bt maize shoots, while concentrations of unsaturated fatty acids were 22.5% higher in non-Bt than in Bt soils. The cumulative CO2-C evolved from soils under Bt and non-Bt crops was 30.5% lower under Bt as compared to non-Bt crops, whereas when maize shoots were added to Bt and non-Bt soils, the decrease in CO2-C evolved were 16.5 and 23.6%, respectively. Our data showed that the cultivation of Bt maize significantly increased the saturated to unsaturated lipid ratios in soils which appeared to negatively affect microbial activity.

Bacillus thuringiensis↗

PubMed1998

Electron paramagnetic resonance and dynamic nuclear polarization of char suspensions: surface science and oximetry.

Carbon chars have been synthesized in our laboratory from a variety of starting materials, by means of a highly controlled pyrolysis technique. These chars exhibit electron paramagnetic resonance (EPR) line shapes which change with the local oxygen concentration in a reproducible and stable fashion; they can be calibrated and used for oximetry. Biological stability and low toxicity make chars good sensors for in vivo measurements. Scalar and dipolar interactions of water protons at the surfaces of chars may be utilized to produce dynamic nuclear polarization (DNP) of the 1H nuclear spin population in conjunction with electron Zeeman pumping. Low-frequency EPR, DNP and DNP-enhanced MRI all show promise as oximetry methods when used with carbon chars.

Biophysical Phenomena↗

PubMed2003

Multifrequency electron spin resonance detection of solid-state organic free radicals in HCN polymer and a Titan tholin.

Macromolecules derived from hydrogen cyanide (HCN) may be major components of the dark matter observed in bodies in the outer Solar System, which include comets and asteroids. HCN oligomers and polymers are readily formed at room temperature and react with water to produce polypeptides and alpha-amino acids or undergo pyrolysis to produce nitrogen heterocycles. Electron spin resonance (ESR) spectroscopy shows that HCN polymer mixtures contain a significant amount of long-lived organic free radicals that are primarily carbon-based. For comparison, we have also examined samples of tholins produced from experimental analogs of Titan aerosols, which has been shown by trace organic analysis to consist partly of HCN polymer. The "Titan tholin" exhibits at least two ESR signals that can be assigned to nitrogen- and carbon-centered radicals, although heating the sample eliminates the nitrogen centers and increases the signal from the carbon centers. This result suggests that the nitrogen-centered radicals may be thermodynamically less stable, but are kinetically trapped during the spark-discharge reactions that produce tholins from mixtures of gases such as methane and nitrogen. The results strongly support previous proposals of free radical mechanisms for HCN polymerization.

Drug Stability↗

PubMed2004

Condensation reactions and formation of amides, esters, and nitriles under hydrothermal conditions.

Hydrothermal pyrolysis experiments were performed to assess condensation (dehydration) reactions to amide, ester, and nitrile functionalities from lipid precursors. Beside product formation, organic compound alteration and stability were also evaluated. Mixtures of nonadecanoic acid, hexadecanedioic acid, or hexadecanamide with water, ammonium bicarbonate, and oxalic acid were heated at 300 degrees C for 72 h. In addition, mixtures of ammonium bicarbonate and oxalic acid solutions were used to test the abiotic formation of organic nitrogen compounds at the same temperature. The resulting products were condensation compounds such as amides, nitriles, and minor quantities of N-methylalkyl amides, alkanols, and esters. Mixtures of alkyl amide in water or oxalic acid yielded mainly hydrolysis and dehydration products, and with ammonium bicarbonate and oxalic acid the yield of condensation products was enhanced. The synthesis experiments with oxalic acid and ammonium bicarbonate solutions yielded homologous series of alkyl amides, alkyl amines, alkanes, and alkanoic acids, all with no carbon number predominances. These organic nitrogen compounds are stable and survive under the elevated temperatures of hydrothermal fluids.

Amides↗

PubMed1998

Carboxyhemoglobinemia due to peritoneal smoke absorption from laser tissue combustion at laparoscopy.

OBJECTIVE: The carbon monoxide (CO) smoke component from tissue pyrolysis was evaluated for peritoneal absorption in patients undergoing laparoscopy to determine its effects and ability to be detected in peripheral blood. SUMMARY BACKGROUND DATA: Previous studies have demonstrated changes in peripheral methemoglobin levels as a result of peritoneal absorption of laser smoke. METHODS: Fifty patients had preoperative, intraoperative, and postoperative levels of carboxyhemoglobin (COHb) and pulse oximetry evaluated. The control group (25) had no laser or cautery used and the study group (25) had carbon dioxide laser used during the laparoscopic procedures. RESULTS: The control group showed no change in COHb, or intra-abdominal CO levels, before, during, and after the procedures, and no change in blood CO or pulse oximetry reading. The laser smoke group showed a statistically significantly elevated (p < .05) peripheral blood COHb levels, a significant increase in intra-abdominal CO concentration, and a lack of correlation of pulse oximetry and blood oxygen saturation experiments. CONCLUSIONS: CO is created in extremely large quantities during laser use at laparoscopy and is absorbed through the peritoneal cavity. Symptoms of smoke poisoning can be seen with these elevations. Continuous or intermittent removal of smoke produced from laser use is recommended.

Absorption↗

PubMed1992

Evaluation of hazards in CO2 laser welding and related processes.

High-power CO2 lasers are used extensively in various industrial applications. In most cases they form part of open-beam equipment and have a power of several kilowatts, and are thus designated as Safety Class 4 systems. In addition to the invisible i.r. laser beam (10.6 microns), u.v. radiation and visible light may be emitted. In the present work a power meter controlled by microprocessor and a spectroradiometer measured the scattered or reflected laser radiation. In addition, concentration levels of welding and cutting fumes and of pyrolysis products of plastics were determined during various laser processes. Finally, a safety analysis was performed to compare the hazards of laser welding with those of conventional welding methods: this showed that the use of laser systems can eliminate many traditional risks, but the worker must be protected not only against the coherent laser beam, but also from incoherent blue light and u.v. radiation.

Air Pollutants, Occupational↗

PubMed1992

Occupational exposure to carbon monoxide and sulphur dioxide during the manufacture of carbon black.

The manufacture of carbon black is known to generate carbon monoxide and sulphur dioxide in the 'production gas' and the pyrolysis products of the 'production gas', respectively. Adverse health effects have been reported as associated with both contaminants (coronary heart disease with carbon monoxide and respiratory morbidity with sulphur dioxide). A major cross-sectional and longitudinal respiratory morbidity study is being conducted to assess the effects of exposure to carbon black on lung function, on chest X-rays and on responses to a questionnaire. The questionnaire includes questions on respiratory and cardiovascular symptoms, so that information regarding confounding exposure is essential. The working population of 18 manufacturing plants in seven European Countries was split into 13 job title numbers (1-13) which were then amalgamated into five job categories (A-E), with an appropriate (statistically) number of samples taken from each plant-job category. In total, 1322 carbon monoxide samples and 1301 sulphur dioxide samples were taken, using actively pumped longterm colorimetric tubes. In the majority of cases, more than half of the samples in each plant-job category were either zero or trace, thereby preventing the accurate estimation of the average exposure. The highest median carbon monoxide concentration was from the amalgamated data from all 18 plants in job number 9 (furnace operators), the highest median sulphur dioxide concentration was only 'trace'. The large number of zero and trace values also precluded the generation of current and retrospective exposure indices.

Air Pollutants, Occupational↗

PubMed1992

Occupational exposure to carbon black in its manufacture.

Carbon black is manufactured by the vapour phase pyrolysis of heavy aromatic hydrocarbon feedstocks. Its manufacture is worldwide and the majority of its production is for use in the rubber industry especially tyre manufacture. Its carbonaceous nature has led many to investigate the occurrence of exposure-related medical conditions. To quantify any such relationships, it is necessary to assess exposure accurately. As part of such an epidemiological investigation survey involving the measurement both of respirable and of total inhalable carbon black was undertaken in 18 plants in seven European countries between mid-1987 and mid-1989. A total of 1298 respirable samples (SIMPEDS cyclone) and 1317 total inhalable samples (IOM head) were taken and deemed of sufficient quality for inclusion in the study. The distributions of the time-weighted average values were assessed and found to be best described by a log-normal distribution, and so exposure is characterized by geometric means and standard deviations. The data are presented in terms of 13 separate job titles for both dust fractions and shows a wide variation between job titles, with the highest mean exposure experienced by the site cleaners, and 30% of the samples taken from the warehouse packers being in excess of the relevant countries' occupational exposure limits for total inhalable dust. The quality and extent of this data allows both for comparison with exposure standards and for generation of occupational exposure indices, which will be presented in another paper (Gardiner et al., in preparation).

Carbon↗

PubMed1989

Prostaglandin hydroperoxidase-dependent activation of heterocyclic aromatic amines.

Heterocyclic aromatic amines, derived from the pyrolysis of amino acids and proteins, are potent mutagens in the Ames Salmonella assay with rodent liver activation. Additionally, heterocyclic aromatic amines are multipotent carcinogens. We report evidence that these compounds are substrates for the hydroperoxidase activity of prostaglandin H synthase, as measured by alterations in UV/visible spectra, and are bioactivated to macromolecule-reactive species by this enzyme. Indirect electron paramagnetic resonance studies indicate that this activation may occur via a one-electron mechanism. 2-Amino-3-methylimidazo[4,5f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) are direct-acting mutagens in TA98. The mutagenicity of IQ and MeIQ, but not Trp-P-2, were enhanced by activation with ram seminal vesicle microsomes (a rich source of prostaglandin H synthase). Subsequent experiments utilized the newly constructed tester strain TA1538/1,8-DNP6 (pYG 121), which has enhanced arylamine N-acetyltransferase activity. In this strain IQ, MeIQ and 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1) were mutagenic with ram seminal vesicle microsome activation. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was a weak direct-acting mutagen, and was not activated by the ram seminal vesicles (RSV) system. The responses of IQ and MeIQ were markedly enhanced in TA1538/1.8-DNP6 (pYG 121), relative to TA98. These data are consistent with the involvement of prostaglandin H synthase-catalyzed activation in heterocyclic aromatic amine-induced extrahepatic neoplasia.

Amines↗

PubMed1989

Photoactivation of mutagens.

Solutions of several promutagens or of non-genotoxic carcinogens were exposed to sunlight or to artificial sources of UV or fluorescent light, under various experimental conditions. Irradiation resulted in the oxygen-mediated formation of direct-acting mutagenic and DNA-damaging photoproducts in bacteria, with evident structure-activity relationship. Of the aromatic amines tested, 2-aminofluorene and, with lower efficiency, 2-acetylaminofluorene were photoactivated, whereas irradiation of 4-acetylaminofluorene and of the 1- and 2-amino substitutes of anthracene and naphthalene did not produce mutagenic derivatives in Salmonella typhimurium. Of the heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline were extraordinarily sensitive to activation by sunlight and fluorescent light, which contrasted with the insensitivity of the tryptophan pyrolysis products. Use of optical and interference filters showed that near-UV light is the main component of solar radiation responsible for the formation of highly stable mutagenic derivatives. The mutagenicity of 2-aminofluorene and of the aminoimidazoquinoline compounds, following both metabolic and light activation, was lost in nitroreductase- and O-acetyltransferase-dificient bacteria. Benzo[alpha]pyrene was better activated by 254- than by 365-nm UV light. Sunlight did not affect the lack of mutagenicity of carcinogenic organochlorine pesticides, but exposure to 254-nm UV light selectively resulted in the formation of weak mutagens from dieldrin and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, but not from 4,4'-dichlorodiphenyltrichloroethane, lacking carbon-carbon double bonds.

DNA Repair↗

PubMed1989

Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus.

The metabolism of chemical carcinogens was investigated in liver preparations from 28 captive woodchucks (Marmota monax). Of these, 23 were naturally infected with the woodchuck hepatitis virus (WHV), and eight also had primary hepatocellular carcinoma (PHC). Twenty-nine parameters were investigated in liver subcellular fractions, including cross-reactivity with HBsAg, and biochemical parameters, such as gamma-glutamyl transpeptidase, cytochrome P-450 and microsomal monooxygenases (aryl hydrocarbon hydroxylase, ethoxycoumarin and ethoxyresorufin deethylases, aminopyrine and dimethylnitrosamine demethylases, and testosterone 7 alpha-, 16 alpha- and 6 beta-hydroxylases), uridine 5'-diphosphoglucuronosyl transferase, GSH and related enzymes (peroxidase, reductase and S-transferase), as well as other cytosolic enzyme activities (glucose 6-phosphate and 6-phosphogluconate dehydrogenases, NADPH- and NADH-dependent diaphorases, and DT diaphorase). In addition, liver preparations were used in order to quantify the metabolic activation into bacterial mutagens of five procarcinogens (aflatoxin B1, the pyrolysis products Trp-P-2 and MeIQ, 2-aminofluorene and dimethylnitrosamine) and the decrease of potency of three direct-acting mutagens (sodium dichromate, ICR 191 and 4-nitroquinoline 1-oxide). WHV infection produced a significant stimulation of carcinogen metabolism, as shown by the simultaneous change in detoxification parameters (GSH depletion) and activation indices (enhancement of microsomal monooxygenases and of procarcinogen activation into mutagenic metabolites). There were no significant differences between WHV-positive samples from animals without PHC and the noncancerous tissue of PHC-bearing animals, whereas a decrease of both activation and detoxification indices was recorded in the tumorous tissue. There was a considerable interindividual variability among WHV carriers, which was tentatively ascribed to genetic factors. Pregnancy was the only known factor influencing the results in WHV carriers. However, even by excluding pregnant animals, the effects on carcinogen metabolism produced by WHV infection were still statistically significant. These results, together with previous data obtained in humans, revealed that metabolic factors may play a role in the synergism between viral hepatitis and chemical hepatocarcinogens in the etiopathogenesis of PHC.

Animals↗

PubMed1989

An efficient and convenient method for the purification of mutagenic heterocyclic amines in heated meat products.

A simple and efficient method for the purification of mutagenic heterocyclic amines from heated meat products has been developed. In only two steps, namely extraction of raw material on Kieselgur followed by medium pressure liquid chromatography on Sephasorb HP, very clean fractions with high recovery rates of mutagenic compounds were obtained, thus allowing isolation and quantitation by high performance liquid chromatography (HPLC) with UV detection. The method was validated on both food grade and bacterial beef extracts as well as fried beef. In 1-5 g samples of beef extracts, levels up to 70 p.p.b. (ng/g) of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 8-90 p.p.b. of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and up to 8 p.p.b. of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) were determined. In fried beef, 1 p.p.b. of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 1 p.p.b. of MeIQx were measured. The quantitative results of beef samples were in agreement with results from determinations using immunoaffinity chromatography/HPLC or liquid chromatography coupled with mass spectrometry. MeIQx could be quantified in fried beef down to 1 ng/g of fresh beef material. According to assays performed with reference standards of tryptophan and glutamic acid pyrolysis products, the method could also be extended to quantitate other heterocyclic amines.

Amines↗

PubMed1989

The food-mutagens 2-amino-1-methyl-6-phenylimidazo-[4,5-b]-pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) initiate enzyme-altered hepatic foci in the resistant hepatocyte model.

The initiating activity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and a mutagenic meat extract obtained from cooked meat was examined, using the resistant hepatocyte model (RH-model). Male Wistar rats were given a single i.p. injection of PhIP (50 or 75 mg/kg body weight) or MeIQx (50 mg/kg body weight) after a 2/3 partial hepatectomy (PH). The meat extract (corresponding to 1050 g meat/animal) was given by gastric feeding at three time points after PH. Two weeks after initiation the rats received a diet containing 0.02% 2-acetylaminofluorene for a period of 2 weeks. In the middle of this period a single dose of carbon tetrachloride was given. Rats were killed 6 weeks after the experimental start. The number of enzyme-altered (gamma-glutamyl-transferase positive) hepatic foci was significantly increased in the animals given MeIQx (P less than 0.05) and the highest dose of PhIP (P less than 0.01) whereas no effect of the meat extract was observed. The mutagenic meat extract was also studied with regard to promotive capacity in vivo, the meat extract was given in the diet of diethylnitrosamine initiated rats for a period of 6 weeks. No significant changes were detected after administration of the meat extract in the diet. It is concluded that both MeIQx and PhIP are weak initiators in the RH-model, in the same order of magnitude as the previously investigated, structurally related pyrolysis products. The meat extract was not active in the RH-model under the conditions used in this study.

Animals↗

PubMed1990

Comparison of initiation potential of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in an in vivo carcinogen bioassay system.

A new approach to low-dose assessment of carcinogenic potential was applied to food contaminant pyrolysis products. Single intragastric doses of the carcinogenic pyrolysates, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline MeIQx), were given 12 h after two-thirds partial hepatectomy (PH) to F344 male rats. Two weeks thereafter the animals were placed on a basal diet containing 0.05% phenobarbital (PB) for 6 weeks combined with an i.p. administration of D-galactosamine (300 mg/kg) to facilitate growth of initiated cells. Both IQ and MeIQx clearly caused initiation of hepatocarcinogenesis as revealed by induction of preneoplastic placental-form glutathione-S-transferase-positive (GST-P+) hepatocyte foci composed of more than three cells (approximately 30 microns in diameter). A similar protocol without performance of PH before pyrolysate administration gave a positive result only for the IQ-treated group indicating that cell proliferation is essential during the low-dose, one-shot initiation step. IQ was found to be two to three times more potent in inducing GST-P+ foci using both protocols. The current approach could find application in practical carcinogenicity screening of chemicals, for which only small amounts are available.

Animals↗

PubMed1993

Mutational specificity of 2-nitro-3,4-dimethylimidazo[4,5-f]quinoline in the lacI gene of Escherichia coli.

2-Nitro-3,4-dimethylimidazo[4,5-f]quinoline (NO2-MeIQ) is the nitro derivative of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), one of the food pyrolysis product mutagens and carcinogens. The mutational specificity of NO2-MeIQ was determined using the lacI system in an Escherichia coli strain, EE125, harbouring the plasmid pKM101. NO2-MeIQ acts as a direct-acting mutagen towards this strain, and induces a broad range of mutational alterations. At higher doses; G:C-->T:A transversions dominate the mutational spectrum. Complex mutations were also observed, and the involvement of the SOS system in the processing of the mutations induced by NO2-MeIQ is suggested.

Bacterial Proteins↗

PubMed1995

Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research.

Heterocyclic amines (HAs) are formed as pyrolysis products during the cooking of meats/fish. These substances are potent mutagens in the Ames/Salmonella assay and are also carcinogens in laboratory animals. In order to assess the magnitude of the cancer risk posed by their presence in the US diet, we estimated the average intakes of HAs, based on analyses of the concentrations of HAs in cooked foods and data from a dietary survey of the US population and quantified the cancer potencies of the individual compounds using dose-response data from animal bioassays. Measured concentrations of HAs in cooked foods were taken from a major review of the open literature. Only those concentrations that were associated with normal cooking conditions were chosen for use in estimating dietary intakes. The average consumption of HA-bearing foods was determined by analyzing statistically the intakes of 3563 individuals who provided 3 day dietary records in a USDA sponsored random survey of the US population during 1989. Dietary intakes of the five principal HAs in descending order were 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) > 2-amino-9H-pyrido[2,3-b]indole (A alpha C) > 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) > 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) > 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The carcinogenic potencies, in contrast, were almost the reverse order: IQ > DiMeIQx > MeIQx > PhIP > A alpha C. An upper-bound estimate of the incremental cancer risk is 1.1 x 10(-4), using cancer potencies based on a body surface area basis. Nearly half (46%) of the incremental risk was due to ingestion of PhIP. Consumption of meat and fish products contributed the most (approximately 80%) to total risk.

Amines↗

PubMed1995

2,3,7,8-Tetrachlorodibenzo-p-dioxin sensitization of cultured human epidermal cells to carcinogenic heterocyclic amine toxicity.

Treatment of cultures of spontaneously immortalized human epidermal cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) sensitized them to carcinogen toxicity. While the tryptophan pyrolysis product 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and the mycotoxin sterigmatocystin were highly toxic to the cultures at moderate concentration (1 microgram/ml), the potency of each agent was increased > or = 10-fold in the presence of TCDD. A toxicity increase was also evident in the several-fold stimulation by TCDD of protein and DNA adducts formed by Trp-P-1. In contrast, the cells were insensitive to toxicity from 3-amino-1-methyl-5H-pyrido[4,3-b]indole. DNA damage mediated by Trp-P-1 was capable of producing inheritable effects, as judged by the induction of hprt mutants in a TCDD-stimulated fashion. Northern blotting showed that TCDD strongly stimulated expression of P4501A1 and 1B1 in the cells, enzymes important for xenobiotic metabolism. These findings demonstrate the potential usefulness of SIK cultures as a model for studying keratinocyte responses to carcinogens activated by TCDD-induced cytochromes P450.

3T3 Cells↗