title: Effect of catechol and ethanol with and without methylamylnitrosamine on esophageal carcinogenesis in the rat.
abstract: Alcohol consumption and cigarette smoking are synergistic etiologic factors for squamous cell carcinoma of the esophagus in Western countries. Catechol, a constituent of cigarette smoke, was previously found to be a co-carcinogen with methyl-n-amylnitrosamine (MNAN) for esophageal tumors in rats, when it was given in the diet. Here we tested whether the inclusion of ethanol in a similar system had an additional promoting effect on esophageal carcinogenesis. Male MRC - Wistar rats were injected three times i.p. with 25 mg MNAN/kg starting from 7 weeks of age. A second group of rats was injected similarly with MNAN and treated for life with 10% ethanol and 0.2% catechol in the drinking water, starting at 6 weeks of age. One or more test chemicals were omitted in other groups. The rats were maintained until they died and were necropsied. The number of esophageal papillomas/rat was 2.18 +/- 0.36, 4.27 +/- 0.53, 2.54 +/- 0.48 and 3.21 +/- 0.52 (mean +/- SE) in groups treated with MNAN alone, MNAN + ethanol + catechol, MNAN + ethanol and MNAN + catechol, respectively. Esophageal carcinomas showed a similar trend, with the number of carcinomas/rat equal to 0.23 +/- 0.08 in the MNAN alone group and 0.50 +/- 0.14 in the MNAN + ethanol + catechol group. Tumor multiplicities for the esophageal papillomas and carcinomas were significantly (P < 0.05) greater in the MNAN + ethanol + catechol group than in the MNAN group. These findings indicate that, in the esophagus, catechol alone was not significantly co-carcinogenic with MNAN when it was given in the drinking water (unlike when given in the diet in our previous study), but that ethanol + catechol given in the water was co-carcinogenic with MNAN. Seven of 19 rats given ethanol + catechol without MNAN developed esophageal papillomas, as compared to zero incidence in untreated controls (P = 0.06). Forestomach papillomas occurred in 22% of all rats given catechol. Hence, for esophageal tumor induction, ethanol and catechol were co-carcinogenic with MNAN and appeared to be tumorigenic when given without MNAN. Ethanol and catechol could have increased the carcinogenicity because they affected MNAN metabolism. As a partial test of this possibility, the effect of feeding these compounds for 5-7 weeks separately or together was examined on 2-, 3-, 4-and 5-hydroxy-MNAN (HO-MNAN) production from MNAN by the esophagus and liver slices from freshly killed rats.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Eppley Institute for Research in Cancer, Omaha, NE.
authors.forename: S S
authors.initials: SS
authors.lastname: Mirvish
authors.forename: D D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: S H
authors.initials: SH
authors.lastname: Hinrichs
authors.forename: J
authors.initials: J
authors.lastname: Nickols
authors.forename: C
authors.initials: C
authors.lastname: Hinman
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced*; D002396:Catechols / Q000633:toxicity*; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D002396:Catechols; D009602:Nitrosamines; C025033:N-amyl-N-methylnitrosamine; D000431:Ethanol; C034221:catechol