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A Castonguay

Publications and source records attributed to A Castonguay.

At least 91 records · Page 5Linked to original sources
PubMed1987

Localization of bound metabolites in the respiratory tissues and oesophagus by high-resolution microautoradiography in Fischer 344 rats treated with N'-nitrosonornicotine.

High-resolution microautoradiography for detection of bound radioactivity in Fischer 344 rats given a single subcutaneous dose of 3H-N'-nitrosonornicotine (3H-NNN) showed a labelling of the olfactory region of the nose, which was restricted to the secretory cells of the glands of the lamina propria mucosae (Bowman's glands). In the oesophagus, bound radioactivity was present in the squamous epithelium, most marked in the middle and superficial cell layers. The olfactory nasal mucosa and the oesophagus are targets for the carcinogenicity of NNN in Fischer 344 rats. Our results indicate that the labelled cells in these tissues are the principal sites in which NNN is activated to alkylating species, and these cells may also be the ones that undergo malignant transformation. Bound radioactivity was also found in the lung (mainly in the Clara cells of the bronchi and bronchioles) and in the trachea (preferentially in the mucous cells), although NNN does not induce tumours in the lung or trachea of the rats. Why covalent binding of metabolites to cellular macromolecules is not correlated to carcinogenesis at these sites is not known.

Animals↗
PubMed1987

Cellular changes induced by the tobacco-specific carcinogen 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone in the respiratory tract of Syrian golden hamsters.

The N-nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) is abundant in cigarette smoke and is a potent pulmonary carcinogen in Syrian golden hamsters. After intratracheal instillation of NNK to Syrian golden hamsters, we observed focal cell death in the trachea and bronchi followed by cellular regeneration. Regenerating cells were not ciliated and led to mucous-cell hyperplasia followed by squamous-cell metaplasia. Lung alterations consisted of bronchiolar hyperplasia with severe dysplastic changes in association with interstitial pneumonitis. NNK induces preneoplastic cellular changes similar to those observed in the pulmonary epithelium of smokers.

Animals↗
PubMed1986

Comparative tumorigenicity and DNA methylation in F344 rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-nitrosodimethylamine.

The tumorigenic activities and DNA methylating abilities in F344 rats of the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the structurally related nitrosamine N-nitrosodimethylamine (NDMA) were compared. Groups of 30 male rats were given 60 s.c. injections of 0.0055 mmol/kg of either NNK or NDMA over a 20-week period (total dose, 0.33 mmol/kg). The experiment was terminated after 104 weeks. The numbers of rats with tumors were as follows for NNK and NDMA, respectively: liver, 10 and 6; lung 13 and 0; and nasal cavity, 6 and 1. NNK was significantly more tumorigenic than was NDMA toward the lung (P less than 0.01) and nasal cavity (P less than 0.05). Groups of rats were treated with a single s.c. injection of 0.39 mmol/kg or 0.055 mmol/kg of NNK or NDMA and the levels of 7-methylguanine and O6-methylguanine were measured in liver, lung, and nasal mucosa 1-48 h after treatment. In liver and lung, levels of 7-methylguanine and O6-methylguanine in DNA were 3-22 times (P less than 0.001) greater in NDMA treated rats than in NNK treated rats. Levels of methylation induced by NDMA and NNK in the nasal mucosa were similar. The results of this study demonstrate that NNK is a more potent tumorigen than NDMA in the F344 rat and suggest that DNA methylation alone does not account for its strong tumorigenicity in rat lung and nasal mucosa.

Animals↗
PubMed1985

Metabolism and tissue distribution of tobacco-specific N-nitrosamines in the marmoset monkey (Callithrix jacchus).

Three male marmoset monkeys (Callithrix jacchus) were injected i.v. with the tobacco-specific carcinogen [2'-14C]N'-nitrosonornicotine (NNN) (20.3 mumol/kg body weight) or [carbonyl-14C]4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (18.8 or 420 mumol/kg body weight). They were sacrificed 4 h later. Tissue distribution was studied in two monkeys by whole-body autoradiography and by computer-assisted densitometric analysis of the autoradiograms. The autoradiograms showed a high level of radioactivity in the liver, nasal mucosa, kidneys, melanin of the eyes, hair-follicles of the skin and in the ceruminous ear glands of the monkeys. Total level of radioactivity was 5.7 times higher in the liver of the [carbonyl-14C]NNK-injected monkey than in that of [2'-14C]-NNN-injected monkey. Washing the sections with trichloroacetic acid and organic solvents selectively removed free metabolites leaving metabolites bound to cellular macromolecules. Level of bound metabolites was 1.5 times higher in the nasal mucosa than in the liver of the [2'-14C]NNN monkey. Levels of bound metabolites were similar in the liver of NNN- and NNK-treated monkeys. The results indicate that the liver and nasal mucosa of C. jacchus can activate NNN and NNK to alkylating species. Unbound metabolites present in the liver, lung, kidneys, eye, blood and urine were extracted and separated by h.p.l.c. Hydroxylation of the carbons alpha to the N-nitroso group of NNN were the major metabolic pathways. Unmetabolized NNN was the major radioactive component in the liver, lung, eye and blood. Reduction of the carbonyl of NNK yields 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol (NNAl). NNAl was present in all tissues analyzed and was the major radioactive component in the eye and stomach lumen. It was also excreted in the urine. NNK and NNAl were metabolized by alpha-carbon hydroxylation. These results suggest that in C. jacchus, NNN, NNK and NNAl are activated to alkylating species by alpha-carbon hydroxylation. In the third monkey injected with NNK, DNA methylation was observed in the liver and nasal mucosa but not in the lung and kidneys. Pulmonary tissues of C. jacchus, unlike those of F344 rats, do not have the enzymic capacities to activate NNK to methylating species.

Animals↗
PubMed1985

Measurement of O6-methyldeoxyguanosine in DNA methylated by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone using a biotin-avidin enzyme-linked immunosorbent assay.

Rabbit antibodies raised against O6-methyl-2'-deoxyguanosine (O6-MedGuo) were used to develop a competitive Biotin-Avidin enzyme-linked immunosorbent assay (BA-ELISA) for the quantitation of this adduct in DNA from animals exposed to tobacco-specific N-nitrosamines. The assay was able to detect as little as 30 mumol O6-MedGuo per mol deoxyguanosine. The specificity of the assay was at least 10 000-fold greater for O6-MedGuo than for unmodified nucleosides or 7-methyl-2'-deoxyguanosine. The sensitivity of the assay was increased to 1 mumol O6-MedGuo per mol deoxyguanosine by the prior separation of O6-MedGuo from unmodified nucleosides by h.p.l.c. This assay was used to study the methylating ability of the tobacco-specific nitrosamine 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats. Four hours after exposure to a single i.v. dose of NNK O6-MedGuo was detected in the target tissues nasal mucosa, lung and liver (219, 13.2 and 34.5 mumol/mol deoxyguanosine) but not in the non-target tissues esophagus, spleen, heart or kidney. Chronic exposure by 14 daily i.p. injections of NNK also resulted in detectable amounts of O6-MedGuo in the lung and nasal mucosa (11.4 and 7.9 mumol/mol deoxyguanosine). These results demonstrate that NNK is capable of methylating DNA in vivo. The methodology developed in these studies will allow us to examine in detail the role of DNA methylation in NNK-mediated carcinogenesis.

Animals↗
PubMed1985

Study of DNA methylation by tobacco-specific N-nitrosamines.

An enzyme-linked immunosorbent assay (BA-ELISA) involving use of biotin-labeled anti-rabbit IgG and avidin-labeled horseradish peroxidase was developed for the measurement of O6-methyl-2'-deoxyguanosine (O6-MedGuo). Up to 5 micrograms of methylated DNA was enzymatically hydrolyzed, and the extent of inhibition of binding of immobilized O6-MedGuo-bovine serum albumin to rabbit anti-O6-MedGuo was measured. Fifty percent inhibition of antigen-antibody binding was achieved with 2.5 pmole of of O6-MedGuo. Separation of O6-MedGuo from unmodified nucleosides by high-performance liquid chromatography (HPLC-BA-ELISA) allowed detection of 700 fmole O6-MedGuo in 1 mg of DNA. Among the tobacco-related carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent. In F344 rats it induces nasal cavity, lung and liver tumors. Four hours after a single IV injection of NNK to F344 rats (87 mg/kg body weight), O6-MedGuo was present in target organs (mumole O6-MedGuo/mole dGuo) (nasal mucosa, 219; lung, 13.2; and liver, 34.5) but was not detectable in nontarget organs. F344 rats receiving daily IP injections of NNK (40 mg/kg body weight) for 14 days were sacrificed 24 hr after the last injection. The levels of (O6-Medguo/dGuo) were 7.9 and 11.4 mumole/mole in the nasal mucosa and lung, respectively. In the liver no O6-MedGuo was detected, but 1050 mumole of 7-MeGua/mole Gua was measured by HPLC-fluorimetry. No DNA methylation was observed in the nasal mucosa or liver of F344 rats treated with the nicotine-derived carcinogen N'-nitrosonornicotine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Microautoradiographic localization of bound metabolites in the nasal cavities of F344 rats treated with the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific N-nitrosamine, labeled with 14C on the carbonyl group, was given iv or orally to F334 rats. The animals were killed 4 hours later, and the localization of bound radioactivity in the nasal cavities was studied by light microscopic autoradiography. The strongest labeling was observed in the following groups of glands situated in the lamina propria mucosae: 1) Bowman's glands in the olfactory region, 2) the group of serous glands situated in the anterior half of the nasal septum beneath the respiratory epithelium, 3) the group of serous glands in the middle portion of the lateral wall of the nasal cavity, and 4) the lateral nasal gland (Steno's gland) located lateroventrally to the maxillary sinus. The group of mucous glands in the septum in connection with Jacobson's organ and the group of glands in connection with the dorsal, medial, and lateral parts of the maxillary sinus were not labeled. The olfactory and respiratory surface epithelia in the various parts of the nasal cavity were only weakly labeled. These results indicate that Bowman's glands, some serous glands, and Steno's glands are the principal sites where NNK is activated to alkylating species.

Animals↗
PubMed1984

Carcinogenicity and metabolic activation of tobacco-specific nitrosamines: current status and future prospects.

Over the past decade, research on the carcinogenicity and metabolism of tobacco-specific nitrosamines has provided a basis for understanding their possible roles in human cancer. 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone appears to be the most important tobacco-specific nitrosamine, because of its strong carcinogenicity. A large population of smokers and snuff dippers is exposed to significant quantities of this and the other tobacco-specific nitrosamines on a daily basis. Further research should now focus on the relationship between human exposure to tobacco-specific nitrosamines and the risk of developing tobacco-related cancers. Several important areas can be identified: we need to develop sensitive assays that can be used routinely to quantify the levels of tobacco-specific nitrosamines or their metabolites in human blood, and the levels of their DNA adducts in human tissues; we need to establish, through comparative metabolic and DNA-binding studies, the relationships between the organospecificity of tobacco-specific nitrosamines in experimental animals and that in humans; we may also be enabled to identify naturally-occurring substances that can inhibit carcinogenesis by tobacco-specific nitrosamines. These research approaches will hopefully lead to a reduction in the incidence of tobacco-related cancers.

Animals↗
PubMed1984

Fate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in pregnant and newborn C57BL mice.

Whole-body autoradiography of pregnant C57Bl mice injected intravenously with the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicated that NNK and/or its metabolites can diffuse through the placenta and reach the fetal tissues. During the last days of gestation, nasal, pulmonary and hepatic tissues develop the enzymatic capacity to activate NNK to alkylating species which bind covalently to cellular macromolecules. Within 4 h of the injection, a considerable proportion of NNK metabolites present in the fetal tissues are excreted in the amniotic fluid via the fetal urinary tract. Incubation of tissue slices with NNK indicated that the nose, the lung and the liver of 13-day-old fetuses could reduce NNK to 4-(methylnitrosamino)-1-(3-pyridyl)butan -1-ol (NNA1), but could not activate NNK by alpha-carbon hydroxylation. However, these activating enzymes were competent in 18-day old fetuses, and the activities increased during the first six days of life. The results provide evidence that NNK could exert genotoxic effects transplacentally and in newborn mice.

Animals↗
PubMed1984

Kinetics of DNA methylation by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in F344 rats.

The carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was injected intravenously (0.41 mmol/kg) into F344 rats. DNA from target organs (lung, liver) and a non-target organ (kidney) was extracted hydrolysed and analysed for methylated guanines by cation-exchange high-performance liquid chromotography-fluorimetry. Levels of O6-methylguanine, a promutagenic lesion, and 7-methylguanine were three to eight times higher in the liver than in the lung. Neither base could be detected in the kidneys. The extent of methylation of hepatic DNA by NNK was 35 times lower than observed with an equimolar dose of NDMA by Swann et al. (1983). The levels of the two methylated guanines in liver and lung DNA increased between 4 and 24 h following NNK injection. NNK is metabolized rapidly in F344 rats to 4-(methylnitrosamino)-1(3-pyridyl)-butan-1-ol (NNA1). The relatively slow methylation of hepatic DNA after injection of NNK could be due to a slow release of methylating species from the major circulating metabolite NNA1. This low but sustained level of O6-methylguanine induced by NNK could, in part, explain its carcinogenic potency.

Animals↗
PubMed1984

Perinatal metabolism of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in C57BL mice.

Whole-body autoradiography of pregnant C57BL mice given iv injections of carbonyl-14C-labeled 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) revealed that some metabolites were covalently bound to cellular macromolecules of the nasal mucosae, bronchial mucosae, and liver of the mother. Unbound metabolites were present in those tissues and were also localized in the gastrointestinal lumens, kidneys, urinary bladder, eye melanin, and corpora lutea of the ovaries. Autoradiograms taken at the 1-hour survival interval showed labeling of the fetal kidneys and urinary bladder. At the 4-hour survival interval, the amniotic fluid was strongly labeled. Chromatography of extracts of tissues obtained from pregnant mice on days 13 and 18 of gestation indicated that unchanged NNK and 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol (NNAI) were present in the placentas and fetal tissues. Some NNK metabolites were covalently bound to tissues of the nose, lung, and liver of 18-day-old fetuses. These results indicate that NNK and NNAI have the capacity to cross the placental barrier and to be activated in fetal tissues. Nasal, pulmonary, and hepatic tissues of 16- and 18-day-old fetuses incubated in vitro with NNK metabolized NNK and NNAI by alpha-carbon hydroxylation. These pathways lead to intermediates able to alkylate cellular macromolecules. The nasal tissues had a higher capacity to alpha-carbon hydroxylate NNK than did pulmonary or hepatic tissues during the last stage of fetal development and during all stages of postnatal life. These results suggest that exposure of C57BL mice to NNK during the last stage of fetal development or during neonatal life could possibly result in development of tumors.

Animals↗
PubMed1984

Effects of chronic ethanol consumption on the metabolism and carcinogenicity of N'-nitrosonornicotine in F344 rats.

The effects of chronic ethanol consumption on the carcinogenicity and metabolism of N'-nitrosonornicotine (NNN) in male F344 rats have been investigated. Groups of 26 to 30 rats were maintained on either a control liquid diet (Groups 1, 3, and 5) or an ethanol-containing liquid diet (Groups 2, 4, and 6) for 4 weeks prior to and during treatment with NNN. The carcinogen was injected s.c. (10 mg/kg, Groups 3 and 4) three times weekly or added to the liquid diet (17.5 mg/liter, Groups 5 and 6). The total dose was 1 mmol of NNN per rat. Control rats (Groups 1 and 2) received s.c. injections of 0.9% NaCl solution. The nasal mucosa was the main target tissue of NNN in Groups 3 and 4, but both the nasal mucosa and esophagus were major target tissues in Groups 5 and 6. In rats treated s.c. with NNN (Groups 3 and 4), ethanol consumption had no effect on the distribution and incidence of nasal cavity tumors. In rats treated with NNN added to the control liquid diet or to the ethanol-containing liquid diet, the number of tumors of the nasal cavity was 18 in Group 5 and 26 in Group 6 (p less than 0.05). In contrast, the number of rats with esophageal tumors was 25 in Group 5 and 20 in Group 6 (p less than 0.05). The effects of ethanol on the enzyme system which activates NNN were studied in rats which had been maintained on an ethanol-containing liquid diet for 4 weeks. Explants of nasal mucosae, lingual mucosae, esophagi , and livers were cultured in vitro with NNN. Nasal mucosae of ethanol-consuming rats had a 1.5-fold higher (p less than 0.05) alpha-carbon-hydroxylating activity than did those of control rats. Activating enzymes in the lingual mucosae, esophagi , and livers were not induced by ethanol. The results show that the increased susceptibility of the rat nasal mucosa to the carcinogenic effects of NNN added to an ethanol-containing diet could be due in part to an induction of activating enzymes by ethanol. However, since chronic ethanol consumption had no apparent effect on the incidence of nasal cavity tumors in rats treated by s.c. injection of NNN, factors other than enzyme induction are important in determining the effects of ethanol on NNN carcinogenicity.

Alcohol Drinking↗
PubMed1983

On the formation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone during smoking.

Tobacco-specific N-nitrosamines (TSNA) are the most abundant carcinogens identified in tobacco and its smoke. Reducing their levels in tobacco products and especially in cigarette smoke is, therefore, a primary goal towards minimizing the carcinogenic burden of the tobacco consumer. This study delineates the mechanisms of formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the most powerful of the carcinogenic TSNA during cigarette smoking. It demonstrates, by means of radiolabeled tracer compounds that 6.9-11.0% of the NNK formed in tobacco during the curing process transfers into the mainstream smoke. This constitutes 26-37% of the NNK present in the smoke. Addition of [methyl-14C]-nicotine to cigarettes, prior to smoking, led to the finding that 0.001% of nicotine in the cigarette column appears in the smoke as NNK. Thus, 63-74% of NNK in smoke is formed during smoking. NNK yield in the smoke was independent of nitrate content of the tobacco. These data serve to devise methods of reducing TSNA in smoke.

Carbon Radioisotopes↗
PubMed1983

Metabolism of tobacco-specific N-nitrosamines by cultured human tissues.

N'-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are present in cigarette smoke and snuff and are carcinogens in laboratory animals. In tobacco smokers, the buccal mucosa, trachea, esophagus, bronchi, and peripheral lung are exposed to smoke containing significant amounts of these N-nitrosamines. The results of the present study demonstrate that explants of these tissues as well as of the urinary bladder have the capacity to metabolize NNN and NNK by alpha-carbon hydroxylation. This metabolic pathway yields alkyldiazohydroxides, which are reactive and DNA-damaging electrophiles. The extent of alpha-carbon hydroxylation of NNN and NNK in human tissues was only 1/10th to 1/100th of that in animal tissues. Although the levels of alpha-carbon hydroxylation of NNN among different tissues of the same individual were similar, a 10-fold variation among individuals was observed. Reduction of the NNK carbonyl group was a major metabolic pathway observed with all human explants and may occur in the surface epithelia of the respiratory tract of smokers. These results provide further evidence that tobacco-specific N-nitrosamines could play a role in cancers related to the smoking and chewing of tobacco.

Biotransformation↗
PubMed1983

The in vivo tissue disposition and in vitro target-tissue metabolism of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in Syrian golden hamsters.

The tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), labeled with 14C in the carbonyl group, was given i.v. or s.c. to Syrian golden hamsters. Whole-body autoradiography indicated that NNK is distributed evenly in the intra- and extracellular tissue water and reaches all tissues. An accumulation of radioactivity was observed in the stomach contents, probably due to the basicity of NNK and its metabolites, which are trapped in the acid gastric juice. The basicity of these compounds is also responsible for their binding to the eye melanin. A high level of tissue-bound metabolites occurred in the mucosa of the ethmoturbinates, in the lungs and in the trachea, which are the targets for the carcinogenicity of NNK in the hamster. In the lungs and the trachea, the radioactivity was confined to the epithelium of the air-conducting ways (the bronchial, bronchiolar and tracheal epithelium). Microautoradiography of the nasal olfactory mucosa showed the highest labeling over Bowman's glands in the lamina propria mucosae. The liver was the only non-target tissue which retained detectable tissue-bound metabolites in vivo. Levels of in vitro degradation of NNK to tissue bound and unbound metabolites were the highest in the nasal mucosa. This tissue as well as the other target tissues - the lung and the trachea - produced considerable amounts of metabolites which are probably derived from alpha-carbon hydroxylations of NNK. In the liver, on the other hand, the main metabolite was a reduction product of NNK. Our results demonstrate that tumorigenesis is correlated with NNK metabolism and binding in the target tissues and support the hypothesis that alpha-carbon hydroxylation is the mechanism of activation of NNK.

Animals↗
PubMed1983

Effects of alpha-deuterium substitution on the mutagenicity of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a carcinogenic tobacco specific nitrosamine, can be converted to electrophilic diazohydroxide intermediates by metabolic hydroxylation of either the methylene carbon (carbon 4) or the methyl carbon attached to the nitrosamine group. To investigate the relative importance of these two processes in NNK mutagenesis, we synthesized 4,4-dideutero-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone([4,4,-D2]NNK) and 4-(trideuteromethylnitrosamino)-1-(3-pyridyl)-1-butanone ([CD3] NNK), and evaluated their mutagenic activities in Salmonella typhimurium tester strains. In the presence of Aroclor induced rat liver 9000 g supernatant, NNK and [4,4-D2]NNK had comparable mutagenic activities towards S. typhimurium TA 1535 and TA 100, but [CD3]NNK was inactive in both strains. These results suggest that hydroxylation of the methyl group of NNK is more important than hydroxylation of carbon 4 in its activation to a mutagen. To test the inherent mutagenicity of 4-oxo-4-(3-pyridyl)butyldiazohydroxide and methyldiazohydroxide which would be formed by methyl hydroxylation or carbon 4 hydroxylation, respectively, we compared the mutagenicities, without activation, of the corresponding model compounds, 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone and carbethoxynitrosaminomethane (methylnitrosourethane). Both compounds were highly mutagenic toward S. typhimurium TA 1535 and TA 100, but at doses of 4 x 10(-3) to 4 x 10(-4) mumol/plate, only 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone was mutagenic. These results are consistent with those obtained with the deuterium substituted compounds and indicate the importance of 4-oxo-4-(3-pyridyl)butylation of DNA in NNK mutagenesis.

Deuterium↗