Detection of tobacco smoke carcinogen-DNA adducts in cultured rat buccal mucosa cells following exposure to ethanol and total cigarette smoke condensate or chewing tobacco

doi:10.1016/0009-2797(92)90058-S

Chemico-Biological Interactions

Volume 85, Issues 2–3, December 1992, Pages 141-150

https://doi.org/10.1016/0009-2797(92)90058-S Get rights and content

Abstract

Formation of carcinogen-DNA adducts in rat oral epithelial cells after treatment with cigarette smoke condensate (CSC) or chewing tobacco in the presence of ethanol was investigated using the ³²P-postlabeling procedure. Concomitant treatment of the cells with ethanol increased the relative adduct level over that found in cells treated with tobacco smoke condensate only. Treatment with chewing tobacco resulted in slightly higher adduct levels than in controls. Treatment of the cells with ethanol did not significantly increase the uptake of a polycyclic aromatic hydrocarbon, benzo[j]fluoranthene, however, high tar CSC alone or in combination with ethanol significantly increased the uptake of radiolabeled benzo[j]fluoranthene, suggesting that increased uptake of the carcinogens may be one of the synergistic mechanisms of alcohol in oral carcinogenesis.

References (28)

D.R. Koop et al.
Purification and characterization of a unique isozyme of cytochrome P-450 from liver microsomes of ethanol-treated rabbits
J. Biol. Chem.
(1982)
P. Müller et al.
Tissue damage in the rabbit oral mucosa by acute and chronic direct toxic activity of different alcohol concentrations
Exp. Pathol.
(1983)
K. Randerath et al.
Age-related DNA modifications (I-compounds): Modulation by physiological and pathological processes
Mutat. Res. Rev. Genet. Toxicol.
(1990)
S. Preston-Martin et al.
Descriptive epidemiology of cancers in the upper respiratory tract in Los Angeles
Cancer
(1982)
W.J. Blot et al.
Smoking and drinking in relation to oral and pharyngeal cancer
Cancer Res.
(1988)
J. Brugere et al.
Differential effects of tobacco and alcohol in cancer of the larynx, pharynx and mouth
Cancer
(1986)
IARC
Alcohol Drinking
J.D. Massey et al.
Smokeless tobacco: a risk factor in oral cancer
Ear, Nose Throat J.
(1984)
M.E. Mattson et al.
Smokeless tobacco: Association with increased cancer risk
NCI Monogr.
(1989)
O.T. Chortyk et al.
A study on the mutagenicity of tobacco smoke from low-tar cigarettes
Arch. Environ. Health
(1990)

N.J. Jones et al.

³²P-Postlabelling analysis and micronuclei induction in primary Chinese hamster lung cells exposed to tobacco particulate matter

Carcinogenesis

(1991)

C.R. Wolf et al.

Molecular genetics of the human cytochrome P-450 system

Biochem. Soc. Trans.

(1990)

R.X. Peng et al.

The induction and competitive inhibition of a high affinity microsomal nitrosodimethylamine demethylase by ethanol

Carcinogenesis

(1982)

H. Autrup et al.

Metabolism of benzo(a)pyrene by cultured rat and human buccal mucosa cells

Carcinogenesis

(1985)

Cited by (14)

PPARγ in head and neck cancer prevention
2014, Oral Oncology
Citation Excerpt :
Preclinical studies support the synergistic effect of tobacco and alcohol. Autrup et al. demonstrated increased uptake of tobacco carcinogens by the oral epithelial cells after exposure to alcohol, as measured by the amount of DNA adducts produced [4]. Clinically, the multiplicative effect of these factors has been demonstrated in several epidemiological studies.
Head and neck cancer is a major source of morbidity and mortality worldwide. Intervention during the early phases of carcinogenesis represents a promising new strategy for curbing the devastating effects of this disease and its primary treatment modalities, surgery and radiation with or without concomitant chemotherapy. This review focuses on the peroxisome proliferator-activated receptor gamma (PPARγ) as a target for chemoprevention of oral cancer. Accumulating data suggest that ligands of PPARγ, which include the thiazolidinedione class of agents approved for the treatment of diabetes, inhibit cancer cell growth in vitro and in animal carcinogenesis models, providing the rationale for testing this approach in populations at risk for head and neck cancer.
Detection of DNA adducts by <sup>32</sup>P postlabeling following chronic exposure of rats to snuff
1997, Cancer Letters
A surgically created canal was used as a reservoir for instillation of snuff into the lower lip of rats for 10 weeks. DNA was isolated and digested with micrococcal nuclease/spleen phosphodiesterase. Polar DNA adducts were detected in all tissues examined when digests were fractionated by high performance liquid chromatography (HPLC), ³²P postlabeled, 3′ dephosphorylated and analyzed by two-dimensional thin layer chromatography (TLC). DNA adducts derived from aromatic carcinogens were not detected when digests were ³²P postlabeled and analyzed by four-dimensional thin layer chromatography. These results suggest that non-aromatic agents initiate carcinogenesis following exposure to snuff. The adduction to DNA in organs of the gastrointestinal tract and the kidneys indicates that snuff usage results in systemic exposure to carcinogens and may contribute to the incidence of neoplasms in organs outside the oral cavity.
Combined effects of ethanol and cigarette smoke on hepatic and pulmonary xenobiotic metabolizing enzymes in rats
1996, Chemico-Biological Interactions
The combined effects of ethanol (EtOH) and cigarette smoke (CS) on hepatic and pulmonary monooxygenase (MO) activities (aniline 4-hydroxylase (AH), aminopyrine N-demethylase (AMND), 7-ethoxyresorufin O-deethylase (EROD), p-nitroanisole O-demethylase (p-NAOD)), lipid peroxidation (LP) and reduced glutathione (GSH) levels and glutathione S-transferase (GST) activities toward several substrates (1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (ENPP)) were determined and compared with those of EtOH or CS alone in rats. When the male adult rats (225–275 g) were treated with 10% EtOH (v/v) in their drinking for 21 days AH, AMND and EROD activities and LP and GSH levels increased significantly whereas GST activity for EAA decreased significantly in liver as compared to controls. EtOH did not change the hepatic p-NAOD and GST activities toward CDNB, DCNB and ENPP. In lung, EtOH increased GST activities toward CDNB and ENPP and LP level but decreased GST activity toward DCNB, significantly. No alterations were noted in pulmonary MO activities and GST activity toward EAA and GSH level by EtOH treatment. When the animals were exposed to CS five times a day, with 1 h intervals, for 3 days in a chamber where smoke and fresh air lead alternatively, AMND, EROD and p-NAOD activities, GST activity toward EAA and GSH level increased but LP level and GST activity for ENPP decreased significantly in liver. CS did not alter the hepatic AH and GST activities toward CDNB and DCNB. In lung, CS increased AH, EROD and p-NAOD activities and LP and GSH levels and decreased all the GST activities studied significantly. CS had no influence on pulmonary AMND activity. For the combined treatment, the animals were treated with 10% EtOH (v/v) in their drinking water for 21 days and during the last 3 days they were exposed to CS five times a day, with 1, h intervals, in a chamber where smoke and fresh air lead alternatively. In these animals, augmentation of elevations were noted in AH and p-NAOD activities and LP and GSH levels but not in EROD and AMND activities in liver. Combined treatment significantly decreased GST activity toward CDNB, ameliorated the alteration caused by either EtOH or CS treatment alone on GST activity toward EAA and potentiated the depression of GST activity toward ENPP to a greater degree. No change was observed in GST activity toward DCNB. In lung, combined treatment potentiated the elevations of AMND and p-NAOD activities and LP level and not those of AH and EROD activities. GST activities toward CDNB, DCNB and ENPP were highly elevated by the combined treatment. No changes were observed in pulmonary GSH level and GST activity for EAA by the combined treatment. These results reveal that the regulations of the hepatic and pulmonary MO and GST are differentially influenced by EtOH, CS and the combined treatment.
Ethanol-induced single-strand DNA breaks in rat brain cells
1995, Mutation Research/Genetic Toxicology
Male Sprague-Dawley rats were intubated with 4 g/kg body weight of ethanol (in a 20%, v/v, water solution). Brain cells were analyzed for single-strand DNA breaks at various post-ethanol administration time points using an alkaline microgel electrophoresis assay. Results showed a significant increase in single-strand DNA breaks in brain cells that peaked at approx. 4 h and returned to control level within 6 h after ethanol administration.
Exposure of human lung cells to tobacco smoke condensate inhibits the nucleotide excision repair pathway
2016, PLoS ONE
Gene expression of CYP1A1 and its possible clinical application in thyroid cancer cases
2016, Asian Pacific Journal of Cancer Prevention

View all citing articles on Scopus

View full text

Detection of tobacco smoke carcinogen-DNA adducts in cultured rat buccal mucosa cells following exposure to ethanol and total cigarette smoke condensate or chewing tobacco

Abstract

J. Biol. Chem.

Exp. Pathol.

Mutat. Res. Rev. Genet. Toxicol.

Descriptive epidemiology of cancers in the upper respiratory tract in Los Angeles

Cancer

Smoking and drinking in relation to oral and pharyngeal cancer

Cancer Res.

Differential effects of tobacco and alcohol in cancer of the larynx, pharynx and mouth

Cancer

Alcohol Drinking

Smokeless tobacco: a risk factor in oral cancer

Ear, Nose Throat J.

Smokeless tobacco: Association with increased cancer risk

NCI Monogr.

A study on the mutagenicity of tobacco smoke from low-tar cigarettes

Arch. Environ. Health

32P-Postlabelling analysis and micronuclei induction in primary Chinese hamster lung cells exposed to tobacco particulate matter

Carcinogenesis

Molecular genetics of the human cytochrome P-450 system

Biochem. Soc. Trans.

The induction and competitive inhibition of a high affinity microsomal nitrosodimethylamine demethylase by ethanol

Carcinogenesis

Metabolism of benzo(a)pyrene by cultured rat and human buccal mucosa cells

Carcinogenesis

³²P-Postlabelling analysis and micronuclei induction in primary Chinese hamster lung cells exposed to tobacco particulate matter