Effects of 7,12-dimethylbenz(a)anthracene on rat mammary epithelial cell macromolecules: a time study

The effects of 7,12-dimethylbenz[a]anthracene (DMBA) on levels of four mammary epithelial cell macromolecules were investigated at various times between 1 and 14 days after Sprague-Dawley virgin female rats were fed the carcinogen. Whereas the level of nuclear protein remained relatively constant throughout this period, comparison with normal controls revealed that significant reductions in nuclear RNA and cytosol protein levels occurred in cells from DMBA-treated animals 24 hours after carcinogen treatment; levels were lowest within the first 3 days. Cytosol protein and nuclear RNA values then increased progressively, reaching normal levels between 4 and 6 days; they were elevated 122% (+/-6 SD) and 41% (+/-5), respectively, above controls by the 14th day. DNA levels remained within normal limits up to the 4th day, after which they gradually increased to 36% (+/-5) above normal by the 14th day. All four macromolecules in neoplastic epithelial cells derived from three mammary adenocarcinomas approximately 135 days after DMBA was fed to rats showed increases similar to, though more pronounced than, those seen in mammary epithelial cells 14 days after carcinogen administration, which suggested that early changes in these macromolecules, especially in RNA and cytosol protein, may be related to DMBA mammary carcinogenesis. The data further suggested that malignant transformation of the epithelial cells may occur within the first 4-6 days, after which there appears to be a loss of normal synthetic control of nuclear DNA, RNA, and cytosol protein.