The binding of 7,12-dimethylbenz(a)anthracene to mammary parenchyma DNA and protein in vivo.

Abstract

Sprague-Dawley female rats were sacrificed at various times after the intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA)-3H. The abdominal-inguinal mammary glands were removed, and the parenchymal cells were separated. Parenchymal cell DNA and protein were isolated, and the DNA was purified by density equilibrium centrifugation in cesium chloride. Sixteen hr after carcinogen feeding, DMBA binding amounted to 47 pmoles/mg of DNA. Fifty % of the DMBA bound to DNA at 16 hr was present 14 days after administration, and 31% was still detectable at 42 days. The amount of DMBA binding to protein was less than one-half that observed bound to DNA. Furthermore, by 14 days, DMBA binding to protein had declined to just detectable levels. Increased parenchymal cell DNA content, due to cellular proliferation resulting from DMBA-induced tumorigenesis, was not responsible for the decreased DNA specific activity observed at 14 and 42 days. Thus, persistent binding of DMBA to rat mammary parenchymal cell DNA in vivo was demonstrated.