Phenotypic variability of chemically induced primary rat mammary tumors

Rat mammary tumors induced by DMBA (7,12-dimethylbenz(a)anthracene) or MNU (N-methyl-N-nitrosourea) were compared for frequency of histological types. Total tumor incidence in 50-day-old rats (Groups 3, 4, 5) was about 100% independently of the rat strain and carcinogen. There were found no distinct histological tumor types between DMBA and MNU carcinogenesis, although the distribution of fibroadenomas, adenocarcinomas and sarcomas varied markedly among rat groups. In 300-day-old female Wistar rats (Group 1) treated with DMBA, fibroadenomas and adenocarcinomas showed an incidence of 58% and 42% respectively. In 50-day-old rats (Group 3) the proportion of adenocarcinomas increased up to 72% of total DMBA tumors. MNU carcinogenesis induced adenocarcinomas in 98% of total tumors in the Lewis rat strain (Group 5), while only 53% in Wistar rats (Group 4). The rest of tumors were sarcomas occurring in opposite ratio to adenocarcinomas. The relatively high susceptibility of connective tissue to MNU as compared with mammary epithelium was due to the mode of MNU administration and seemed to be strain dependent. Both DMBA and MNU carcinogenic systems are valuable experimental models of mammary tumor. The cell phenotypes of the resulting tumors can be predicted with high probability by the choice of dose regimen of carcinogen and the route of its application.