MEDROXYPROGESTERONE ACETATE ACCELERATES THE DEVELOPMENT AND INCREASESTHE INCIDENCE OF MOUSE MAMMARY-TUMORS INDUCED BY DIMETHYLBENZANTHRACENE

Chemical induction of mammary tumors in mice requires usually a long l atency period and is often complicated by high non-mammary tumor relat ed mortality, Classically hormone stimulation has been used as the mea ns to increase tumor incidence, The synthetic progestin medroxyprogest erone 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, I n our study we tested the use of a protocol of combined MPA- and dimet hylbenz[a]anthracene (DMBA) treatment for the obtention of mammary tum ors with a short latency and with a lower toxicity than the classical multiple dose DMBA protocol, MPA was very effective in accelerating th e development and increasing the incidence of mammary tumors induced b y DMBA in CD2F1 mice, MPA by itself did not produce any mammary tumors . The mean latency for tumor development from the end of carcinogen tr eatment was 99 +/- 51 days in the group that received a combination of MPA and four DMBA doses, This group showed significantly earlier mamm ary tumor incidence (P < 0.0001) and higher tumor numbers than the gro ups that received only DMBA, Mammary tumors were also analyzed for eff ects on the mutation rate affecting the Ha-ras and Ki-ras genes, Our d ata is consistent with MPA probably increasing the number of target ce lls at risk for mutation by the chemical carcinogen DMBA and possibly promoting the faster development of tumors.