Rapid induction of mammary cancer by repeated subcutaneous injection of the trans-3,4-dihydrodiol of 7,12-dimethylbenz[a]anthracene in the female Sprague–Dawley rat

The oral administration of a single 20 mg dose of 7,12-dimethylbenz[a]anthracene regularly and rapidly induces mammary cancer in 50 day-old Sprague–Dawley female rats [Experimental Leukemia and Mammary Cancer, 1979, p. 74]. Several mechanisms by which 7,12-dimethylbenz[a]anthracene induces mammary cancer have been proposed and various derivatives have been implicated as possible proximate or ultimate electrophilic and carcinogenic forms of this hydrocarbon. Here we show that 7,12-dimethylbenz[a]anthracene-trans-3,4-dihydrodiol rapidly induces mammary cancer by repeated subcutaneous injection in a high proportion of female Sprague–Dawley rats without malignancies at the site of injection, whereas its more lipid soluble diacetate derivative induced injection site sarcomas in addition to distal mammary cancers. By contrast, repeated subcutaneous injection of 7,12-dimethylbenz[a]anthracene and its 7-meso-aldehyde derivative induced subcutaneous sarcoma in most, if not all, rats and a few mammary cancers.