Female Sprague-Dawley rats were given by stomach tube 7,12-dimethylbenz[a]
anthracene [(DMBA) CAS: 57-97-6] on the 77th day of age at the rate of 1.6 mg/100 g
body weight, or
procarbazine [(PCZ) CAS: 671-16-9] on the 84th day of age at the rate of 10 mg/100 g
body weight, or 0.5 Gy of total-body x-rays on the 91st day of age, singly or in all possible combinations or no treatment. All rats were studied for mammary
carcinogenesis for 370 days after the 84th day of age. Three measures of mammary
carcinogenesis were studied. These were the incidence of rats with mammary
adenocarcinomas, or mammary
fibroadenomas, or mammary
neoplasia of either type. Each of these measures was studied also for rats with 2 or more or 3 or more
mammary neoplasms. Assessment of possible interaction among the three
carcinogens with regard to the incidence of
neoplasms was done by time-independent or time-dependent methods, both of which gave remarkably consistent results. For rats with 1 or more
adenocarcinomas, 1 or more
fibroadenomas, or 1 or more
adenocarcinomas and/or
fibroadenomas, both methods showed no interaction among the
carcinogens, which can, therefore, be considered to have produced additive effects. An exception to this finding of additivity was an apparent synergistic interaction between DMBA and PCZ when the measures of rats with 2 or more, or 3 or more
mammary neoplasms of either type, or 3 or more
fibroadenomas were analyzed; these analyses, however, were based on relatively small numbers of rats with multiple
tumors. Since no interactions were found for the usual measure of
carcinogenesis, namely, incidence of rats with 1 or more
neoplasms, the overall conclusion is that DMBA, PCZ, and x-ray act additively in the induction of
mammary neoplasms in the female Sprague-Dawley rat.