It is important to identify not only carcinogenic agents but also to identify factors that modulate the susceptibility of man to carcinogens. Numerous epidemiological studies have implicated alcohol as either a direct or indirect acting carcinogen, primarily as a possible cause of cancers of the oropharynx, esophagus and liver. More recent data have also shown a positive correlation between alcohol consumption and breast cancer in women. The purpose of this proposal is to develop animal tumor models that confirm the epidemiological data (i.e., show and enhancement of carcinogenesis by ethanol and/or alcoholic solutions). Previous studies to establish animal models for this purpose have not been highly successful, possibly due to the method by which alcoholic solutions were administered to the animals. Since known quantities of alcoholic solutions can be given by intragastric intubation, it is felt that this route of administration is preferable for the proposed in vivo carcinogenesis studies. The animal models selected will use 1-methyl-1-nitrosourea (MNU) and dimethylbenzanthracene (DMBA) for the induction of mammary cancer and methylbenzylnitrosamine (MBZN) for the induction of esophageal cancer. Specific studies are designed to determine the effect of ethanol on the different stages of the carcinogenic process; i.e., initiation and promotion. In addition, the effect of two alcoholic beverages (whiskey and wine) will be evaluated in the esophageal cancer model. If ethanol or alcoholic beverages enhance carcinogenesis in these models, additional studies relative to their mechanism(s) of action will be warranted.
