The effect of age on the histopathogenesis of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in the Lewis rat.

The influence of age at time of DMBA administration on (1) the histopathogenesis and site of mammary tumor origin and (2) the precancerous nature of DMBA-induced mammary dysplasias was examined in Lewis rats between 25 and 200 days of age. Rats were killed at various times after carcinogen treatment and the numbers of tumors and dysplasias were recorded from microscopic examination of mammary gland wholemounts. We found that, in all age-groups tested, mammary tumors always appeared to originate within mammary end-buds and terminal ductules and that terminal ductule hyperplasia appeared to be an early stage in tumor formation. Age-related differences in susceptibility to tumor development were paralleled by similar differences in susceptibility to the development of terminal ductule hyperplasias. In contrast, although age-related differences in susceptibility to the development of hyperplastic alveolar nodules were also noted, they did not correspond to those observed for tumor development. Thus, hyperplastic alveolar nodules did not appear to be a site of tumor origin in situ or directly related to tumor development.