Enhancement by Chronic Ethanol Intake of N-methyl-N-nitrosourea-induced Rat Mammary Tumorigenesis

A majority of epidemiological investigations report an association between risk for breast cancer in women and alcohol consumption. However, evidence for an enhancing effect of ethanol on chemically induced rat mammary tumorigenesis is limited and inconsistent. The present study was conducted to evaluate the influence of low to high ethanol intakes (15, 20 or 30% of calories) as part of a defined, liquid diet on both the initiation and promotion stages of N-methyl-N-nitrosourea (MNU)-induced rat mammary tumorigenesis. Ethanol consumed by rats at 15% of calories during either the initiation or promotion stages increased the number of mammary adenocarcinomas compared to isocaloric controls. Ethanol intake at 20% of calories only during the promotion stage resulted in an increase in the number of mammary adenocarcinomas compared to controls. No enhancing effect of dietary ethanol at 30% of calories on either stage of tumorigenesis was observed in comparison to isocaloric controls. Therefore, ethanol at specific intakes can enhance the initiation and promotion stages of MNU-induced rat mammary tumorigenesis. There was not, however, a corresponding increase in mammary tumor development at the highest intake of ethanol evaluated. Possible reasons for this latter lack of effect of ethanol are discussed.