Causative Factors for Refractoriness of Parous Rats to Mammary Carcinogenesis

Parous Rats Treated with MNU Have a High Incidence of Latent Mammary Cancers. In collaboration with Dr. Airo Tsubura, the role ofparity before and after MNU treatment was studied (24). Pregnancy and lactation before (22%) or after (25%) MNU treatment reduced the incidence of frank MCs compared to age-

matched nulliparous females (72%) and (94%), respectively. At termination, rats that underwent pregnancy prior to MNU (67%) or after MNU (50%) both had high incidences of microscopic latent mammary cancers. These findings suggest that MCs are initiated at a fairly high incidence in parous rats, but many ofthese cancers do not progress to frank MCs during the 12 mo after MNU treatment. Thus, these studies indicate that the MEC are highly susceptible to initiation of carcinogenesis and are not completely refractory to the carcinogenic process.

Refractoriness to Frank Mammary Carcinogenesis in Parous Rats can be Overcome by Hormone Treatment. In a separate study, MNU was given to parous rats or parous rats treated with 20 |ig E2 or 20 mg P or E2 + P in silastic capsules for 7 days followed by continuous promotional treatment with E2, P, or E2 + P in silastic capsules (25). 10% of parous rats not treated with promotional hormone developed MCs. 67% ofthose treated with E2,50% of the rats treated with P, and 92% ofthose treated with E2 + P developed MCs. These results show that the parity refractoriness to MNU can be reversed by treatment with ovarian steroids that increase proliferation in the mammary gland.

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