Chemical induction of mammary
tumors in mice requires usually a long latency period and is often complicated by high non-mammary
tumor related mortality. Classically
hormone stimulation has been used as the means to increase
tumor incidence. The
synthetic progestin medroxyprogesterone acetate (MPA) was postulated by some authors to increase mammary
tumor incidence in various rodent models. However, controversy exists regarding the role of MPA in experimental and human
carcinogenesis. In our study we tested the use of a protocol of combined MPA- and dimethylbenz[a]
anthracene (DMBA) treatment for the obtention of mammary
tumors with a short latency and with a lower toxicity than the classical multiple dose DMBA protocol. MPA was very effective in accelerating the development and increasing the incidence of mammary
tumors induced by DMBA in CD2F1 mice. MPA by itself did not produce any mammary
tumors. The mean latency for
tumor development from the end of
carcinogen treatment was 99 +/- 51 days in the group that received a combination of MPA and four DMBA doses. This group showed significantly earlier mammary
tumor incidence (P < 0.0001) and higher
tumor numbers than the groups that received only DMBA. Mammary
tumors were also analyzed for effects on the mutation rate affecting the Ha-ras and Ki-ras genes. Our data is consistent with MPA probably increasing the number of target cells at risk for mutation by the chemical
carcinogen DMBA and possibly promoting the faster development of
tumors.