Effect of catechol and ethanol with and without methylamylnitrosamine on esophageal carcinogenesis in the rat.
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)
Mirvish
S S
SS
Eppley Institute for Research in Cancer, Omaha, NE.
Weisenburger
D D
DD
Hinrichs
S H
SH
Nickols
J
J
Hinman
C
C
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
D002273:Carcinogens; D002396:Catechols; D009602:Nitrosamines; C025033:N-amyl-N-methylnitrosamine; D000431:Ethanol; C034221:catechol