Biomedical subjects

S S Hecht

Publications and source records attributed to S S Hecht.

At least 253 records · Page 14Linked to original sources

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

Metabolism of 1-nitro[U-4,5,9,10-14C]pyrene in the F344 rat.

1-Nitro[U-4,5,9,10-14C]pyrene was synthesized and administered to male F344 rats by intragastric gavage at a dose of 100 mg/kg of body weight. During the first 48 hr, 41% of the dose was eliminated in the feces, and 16% was eliminated in the urine. The corresponding figures after 120 hr were 51 and 19%. In rats with bile cannulae, 37% of the dose was excreted in the bile after 72 hr, and 6% was excreted in the urine. Fecal metabolites included 1-aminopyrene (isolated amount, 11.7% of the dose), 1-amino-6-hydroxypyrene and 1-amino-8-hydroxypyrene (4.6%), and unchanged 1-nitropyrene (6.6%). 1-Aminopyrene and the 1-aminohydroxypyrenes were identified as their acetyl-derivatives by comparison of their chromatographic retention times, mass spectra, and UV spectra to those of synthetic standards. Biliary metabolites included 1-aminopyrene, 1-amino-6-hydroxypyrene, 1-amino-8-hydroxypyrene, 1-nitro-6(8)-hydroxypyrene, and 1-nitro-3-hydroxypyrene, as well as their glucuronide and sulfate conjugates. The isolated amounts of these metabolites accounted for approximately 5% of the dose. 1-Amino-6-hydroxypyrene and 1-amino-8-hydroxypyrene and their glucuronide and sulfate conjugates were also tentatively identified in the urine and accounted for about 3% of the dose. Significant quantities of unidentified water soluble metabolites were present in the urine and bile. The results of this study indicate that metabolic reduction of the highly mutagenic 1-nitrohydroxypyrenes occurs in vivo in the rat and suggest that this is a possible activation pathway in 1-nitropyrene carcinogenesis.

Animals↗

PubMed1984

A sensitive new method for the detection of N-nitrosomorpholine formation in vivo.

A sensitive method was developed for quantitation of N-nitrosomorpholine (NMOR) formation in vivo in rats. A major metabolite of NMOR, N-nitroso(2-hydroxyethyl)glycine, was detected by gas chromatography-thermal energy analysis in the urine of rats treated with trace levels of NMOR or treated sequentially with morpholine and sodium nitrite. Since significant levels of 2-hydroxyethylglycine do not seem to occur in rat urine, even after treatment with morpholine, artefact formation was not a problem. Formation of 1 micrograms NMOR in vivo was readily detected. The formation of NMOR from morpholine and sodium nitrite in vivo in rats appeared to depend on the doses of morpholine and [sodium nitrite]2 and occurred in higher yield than reported for formation of N-nitrosoproline, as expected. The formation of NMOR from morpholine and sodium nitrite under the conditions of the carcinogenicity study of Shank and Newberne was quantified. The daily levels of NMOR formation were highly variable, but the mean level was consistent with the tumorigenicity data in that dose-response study.

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

Inhibition of target tissue activation of N'-nitrosonornicotine and N-nitrosopyrrolidine by dietary components.

Twenty-one dietary and related chemicals have been evaluated for their potential inhibitory activities against the tumorigenic effects of N-nitrosopyrrolidine and N'-nitrosonornicotine using in-vitro metabolic assays in the target tissues, namely, rat liver microsomes and cultured rat oesophagus, respectively. Compounds studied include phenols, cinnamic acids, coumarins, isothiocyanates and indoles. Isothiocyanates were the most potent inhibitors of both nitrosamines in the acute studies, but were less active in chronic studies. This difference may be explained by the pharmacokinetic properties of these compounds. Phenols, cinnamic acids, coumarins and indoles were primarily inducers of N-nitrosopyrrolidine metabolism. The results suggest that isothiocyanates, in general, are the most promising chemicals for future study as protective agents against the carcinogenic effects of these nitrosamines.

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

Identification of the major adducts formed by reaction of 5-methylchrysene anti-dihydrodiol-epoxides with DNA in vitro.

5-Methylchrysene is metabolically converted to the bay-region dihydrodiol-epoxides, trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I), in which the methyl group and the epoxide ring are in the same bay region, and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (DE-II). Previous studies have indicated that DE-I is more important in 5-methylchrysene carcinogenesis than is DE-II. Both DE-I and DE-II were individually reacted with calf thymus DNA in vitro. The DNA was enzymatically hydrolyzed to deoxyribonucleosides, and the modified deoxyribonucleosides were separated by chromatography on Sephadex LH-20 and analyzed by high-performance liquid chromatography. One major adduct and seven minor adducts were formed from each dihydrodiol-epoxide. The major adduct was, in each case, characterized by its pH-dependent partition coefficient, stability to base, mass spectrum, ultraviolet spectrum, and nuclear magnetic resonance spectrum as a deoxyguanosine derivative resulting from addition of the exocyclic amino group of deoxyguanosine to the benzylic carbon of the epoxide ring of the dihydrodiol-epoxide. The results of this study show that the major DNA adducts formed from 5-methylchrysene via DE-I and DE-II are structurally similar.

Animals↗

PubMed1984

Inhibition by a peri-fluorine atom of 1,2-dihydrodiol formation as a basis for the lower tumorigenicity of 12-fluoro-5-methylchrysene than of 5-methylchrysene.

12-Fluoro-5-methylchrysene, which has a fluorine atom at a peri position, is less carcinogenic toward mouse skin than is 5-methylchrysene. To determine the basis for this observation, we identified metabolites of 12-fluoro-5-methylchrysene formed by rat liver in vitro, and used these as standards to study the metabolism of [3H]-12-fluoro-5-methylchrysene in mouse liver in vitro and in mouse epidermis in vivo. Metabolites were identified by their ultraviolet, mass, and nuclear magnetic resonance spectra, by comparison to synthetic standards, and by chemical transformations. Dihydrodiols, phenols, and hydroxymethyl derivatives of 12-fluoro-5-methylchrysene were characterized. The extents of formation of 1,2-dihydro-1,2-dihydroxy-12-fluoro-5-methylchrysene and 7,8-dihydro-7,8-dihydroxy-12-fluoro-5-methylchrysene in mouse liver in vitro were strongly influenced by pretreatment with 3-methylcholanthrene, but the ratio of 1,2-dihydrodiol to 7,8-dihydrodiol was lower than in the metabolism of 5-methylchrysene carried out under identical conditions. The major metabolites of [3H]-12-fluoro-5-methylchrysene formed in mouse epidermis, 0.33 to 4 hr after topical application, were 7,8-dihydro-7,8-dihydroxy-12-fluoro-5-methylchrysene and 7-hydroxy-12-fluoro-5-methylchrysene. The ratio of 7,8-dihydro-7,8-dihydroxy-12-fluoro-5-methylchrysene to 1,2-dihydro-1,2-dihydroxy-12-fluoro-5-methylchrysene in mouse epidermis, 2 hr after application of [3H]-12-fluoro-5-methylchrysene, was 68:1, compared to 1:1 for the corresponding dihydrodiols of 5-methylchrysene. These results show that fluorine substitution at the 12-peri position of 5-methylchrysene inhibits formation of the 1,2-dihydrodiol in the adjacent ring. Since the 1,2-dihydrodiol is a major proximate carcinogen of 5-methylchrysene, the results provide an explanation for the relatively low carcinogenicity of 12-fluoro-5-methylchrysene.

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↗

PubMed1984

A sensitive method for detecting in vivo formation of N-nitrosomorpholine and its application to rats given low doses of morpholine and sodium nitrite.

A method was developed to monitor the in vivo formation of N-nitrosomorpholine. N-Nitroso(2-hydroxyethyl)glycine, a major urinary metabolite of N-nitrosomorpholine, was quantified as its methyl ester-trimethylsilyl ether derivative, using gas chromatography with nitrosamine-specific detection. When the method was applied to rats, the in vivo formation of, or exposure to, as little as 0.6 micrograms of N-nitrosomorpholine could be quantified. The method was also applicable to human urine, with a detection limit of approximately 0.5 micrograms of N-nitroso(2-hydroxyethyl)glycine per 100-ml urine sample. The formation of N-nitrosomorpholine was measured in rats treated by gavage with a wide range of doses of morpholine and NaNO2. Depending on the dose, 0.5 to 12% of the morpholine was nitrosated. N-Nitrosomorpholine formation showed a high degree of variability among rats treated with a given dose of morpholine and NaNO2, but the levels of N-nitrosomorpholine formed were generally in agreement with expectations based on in vitro studies in which dependence on morpholine concentration multiplied by nitrite concentration squared has been established. The formation of N-nitrosomorpholine was also measured in rats administered a diet containing 50 ppm of morpholine and 1000 ppm of NaNO2, a regimen which has been previously shown to induce liver cell tumors in 58% of the animals. The mean daily formation of N-nitrosomorpholine under these conditions was estimated to be 0.88 +/- 0.59 mumol/rat (S.D.), which is high enough to account for the observed tumor incidence. The results of this study provide quantitative support for the assumption that in vivo formation of N-nitrosomorpholine leads to tumor development.

Animals↗

PubMed1984

Effects of dietary compounds on alpha-hydroxylation of N-nitrosopyrrolidine and N'-nitrosonornicotine in rat target tissues.

Male F344 rats were pretreated with various dietary compounds, and the effects of pretreatment on the in vitro alpha-hydroxylation of N-nitrosopyrrolidine or N'-nitrosonornicotine were determined in assays with liver microsomes or cultured esophagus, respectively. Dietary compounds included phenols, cinnamic acids, coumarins, indoles, and isothiocyanates. Pretreatments were carried out either by administering the compound by gavage 2 hr prior to sacrifice (acute protocol) or by adding the compound to the diet for 2 weeks (chronic protocol). Acute pretreatment with benzyl isothiocyanate, allyl isothiocyanate, phenethyl isothiocyanate, phenyl isocyanate, and benzyl thiocyanate but not sodium thiocyanate inhibited formation of alpha-hydroxylation products of both nitrosamines. When the chronic pretreatment protocol was used, only phenyl isothiocyanate and sodium thiocyanate inhibited formation of alpha-hydroxylation products of both nitrosamines. Pretreatments with butylated hydroxyanisole, p-methoxyphenol, or N-acetylcysteine had little, if any, effect on the alpha-hydroxylation of N-nitrosopyrrolidine or N'-nitrosonornicotine. Chronic pretreatment with p-hydroxycinnamic acid, 4-hydroxy-3- methoxycinnamic acid, coumarin, umbelliferone, limetine , indole, indole-3-carbinol, indole-3-acetonitrile, and L-tryptophan induced activity for the alpha-hydroxylation of N-nitrosopyrrolidine. The results of this study indicate that isothiocyanates are possible candidates for further study as potential inhibitors of carcinogenesis by N-nitrosopyrrolidine and N'-nitrosonornicotine.

Animals↗

PubMed1983

N-nitroso-N-methyloctadecylamine in hair-care products.

Fifty-three cosmetic products containing one or more of the ingredients N,N-dimethyloctadecylamine oxide, N,N-dimethyloctadecylamine and N-benzyl-N,N-dimethyloctadecylammonium chloride were analysed for N-nitroso-N-methyloctadecylamine by gas chromatography with detection by a Thermal Energy Analyzer. [1-14C]N-Nitroso-N-methyloctadecylamine was used as an internal standard. Eight of 11 products containing N,N-dimethyloctadecylamine oxide and three of 38 products containing N-benzyl-N,N-dimethyloctadecylammonium chloride were found to contain N-nitroso-N-methyloctadecylamine at levels ranging from 28 to 969 ppb. In photolysis experiments, all of these products exhibited a loss of Thermal Energy Analyzer response for N-nitroso-N-methyloctadecylamine following irradiation by ultraviolet light. In two cases, the presence of N-nitroso-N-methyloctadecylamine was confirmed by combined gas chromatography-mass spectrometry.

Chromatography, Gas↗

PubMed1983

Comparative carcinogenicity in F344 rats and Syrian golden hamsters of N'-nitrosonornicotine and N'-nitrosonornicotine-1-N-oxide.

N'-Nitrosonornicotine (NNN) or N'-nitrosonornicotine-1-N-oxide (NNN-1-N-oxide), one of its metabolites, was added to the drinking water (0.012% for 36 weeks) of groups of male and female F344 rats or to the drinking water (0.016% for 31 weeks) of groups of male and female Syrian golden hamsters. All rats treated with NNN had died after 12 months but 50% of those treated with NNN-1-N-oxide survived for 22 months. NNN induced esophageal tumors in 23/24 rats and nasal cavity tumors in 21/24 rats. NNN-1-N-oxide induced esophageal tumors in 10/24 rats and nasal cavity tumors in 18/24 rats. There was no difference in survival rates among hamsters treated with either NNN or NNN-1-N-oxide. NNN induced tracheal tumors in 2/20 hamsters and nasal cavity tumors in 4/20 hamsters. NNN-1-N-oxide did not induce respiratory tract tumors in hamsters. These results demonstrate that NNN-1-N-oxide is less carcinogenic than NNN in F344 rats and Syrian golden hamsters.

Animals↗

PubMed1983

Bioassay for carcinogenicity of 3,2'-dimethyl-4-nitrosobiphenyl, O-nitrosotoluene, nitrosobenzene and the corresponding amines in Syrian golden hamsters.

3,2'-Dimethyl-4-aminobiphenyl and 3,2'-dimethyl-4-nitrosobiphenyl were administered by subcutaneous injection in peanut oil to 2 groups of 15 male and 15 female Syrian golden hamsters. The total dose of each compound was 5.6 mmol/kg. In the group treated with 3,2'-dimethyl-4-aminobiphenyl, 24 animals had bladder tumors. In the group treated with 3,2'-dimethyl-4-nitrosobiphenyl 25 animals had subcutaneous tumors and 2 had bladder tumors. These results indicate that 3,2'-dimethyl-4-nitrosobiphenyl is a potent locally acting carcinogen. Total doses of 99 mmol/kg of aniline, o-toluidine, nitrosobenzene, or o-nitrosotoluene administered by subcutaneous injection failed to induce tumors.

Animals↗

PubMed1983

The role of intestinal microflora in the metabolic reduction of 1-nitropyrene to 1-aminopyrene in conventional and germfree rats and in humans.

1-Nitropyrene (100 mg/kg body wt.) was administered by gavage to conventional and germfree Fischer 344 rats. 1-Aminopyrene was detected in the feces of conventional rats (5-6% of the dose) but not in the feces of germfree rats. Conjugates of 1-aminopyrene were not detected in the feces of germfree rats and neither 1-aminopyrene nor its conjugates were found in the urine of either conventional or germfree rats. Since reduction of 1-nitropyrene to 1-aminopyrene is an activation process, the results indicate that intestinal microflora are important in the metabolic activation of 1-nitropyrene in vivo in the rat. Human intestinal microflora also reduced 1-nitropyrene to 1-aminopyrene.

Anaerobiosis↗

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

Induction of respiratory tract tumors in Syrian golden hamsters by a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the effect of smoke inhalation.

Four groups of 10 male and 10 female Syrian golden hamsters were given single s.c. injections of either 0.3 ml of trioctanoin or of 0.3 ml of trioctanoin containing either 1.0 mg, 3.3 mg, or 10.0 mg of the tobacco specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These hamsters were then exposed to cigarette smoke for the next 72 weeks. Four control groups received the same injections of NNK or trioctanoin but were treated by sham smoking. All groups treated with NNK had tumors of either the lung, nasal mucosa, and/or trachea. These tumors were not observed in hamsters injected with trioctanoin. These results demonstrate that even a single dose of NNK can induce respiratory tract tumors in Syrian golden hamsters. Smoke inhalation did not result in an increase in respiratory tract tumor incidence in most of the NNK treated groups.

Animals↗