Carcinogenic responses to chemicals applied directly to rat mammary glands in situ

In four experiments, concentrated glycerin suspensions of 7,12-dimethylbenz[a]anthracene (DMBA), or the water-soluble compounds, N-methyl-N-nitrosourea (MNU), N-ethyl-N-nitrosourea (ENU), and 4-nitroquinoline-N-oxide (4-NQO) were delivered into pockets in the mammary fat pads in female Sprague-Dawley rats. In a 90-day experiment, each of three groups of 20-22 rats were treated with either 25, 50 or 100 micrograms DMBA delivered to each of four sites in each rat per group. Dose-related responses were detected for incidence of rats with mammary adenocarcinoma (MAC), and for number of MAC per treated site. In a 120-day study, each of three groups of 20 animals were treated with either 250, 500 or 1000 micrograms MNU at each of 80 sites per group. Dose-related MAC responses were detected for incidence of rats with MAC, number of MAC per treated site, and time to detection of MAC. In two experiments of 90 days duration, groups of 20 females were treated with either 1000 micrograms ENU or 1000 micrograms 4-NQO at each of 80 sites per group. ENU produced a total of 27 MAC sites in 65% of the rats, and 4-NQO produced a total of 26 MAC in 60% of the rats. A comparison of the time to detection of all MAC data for the three water-soluble compounds at the 1000 micrograms treatment level, or on the basis of moles per treatment, yielded a carcinogenic potency relationship of 4-NQO greater than ENU greater than MNU.