Evidence of separate pathways for viral and chemical carcinogenesis in c3h/stwi mouse mammary glands

Mammary tumors in mice may arise as the result of exogenous infection with the mouse mammary tumor virus MMTV(S)], usually via the milk; by the action of endogenous MMTV genes which are transmitted genetically and are sometimes expressed as infectious virus MMTV(L)]; or by the action of chemical carcinogens. We have examined the etiological relationship between chemical and virus in the induction of mammary cancer in C3H/StWi mice. Mammary tumors were induced with 7.12-dimethylbenz(a)anthracene (DMBA) in virgin C3H/StWi mice infected with exogenous mouse mammary tumor virus (C3H/StMTV) and in uninfected C3H/StWi females. The percent tumor risk in females whose glands were infected with exogenous mouse mammary tumor virus MMTV(S)] was not different from that of MMTV(S)-negative, C3H/StWi mice following treatment with DMBA. This result suggested that there was no synergistic effect between the two carcinogens, exogenous MMTV and Dmba. All the tumors arising in DMBA-treated C3H/StMTV virgins were positive for MMTV env gene product, gp52 and MMTV gag gene product, p²⁷ by radioimmune competition assay. MMTV(S)-induced hyperplastic alveolar nodules (HAN) were observed in 62 % of the untreated C3H/StMTV glands at 8 months of age. Therefore, MMTV(S) was present and active in the mammary gland during the experimental period but had no enhancing influence on the sensitivity of the gland to carcinogenesis by DMBA. Tumors appearing in DMBA-treated C3H/StWi virgin females were also tested for MMTV gp⁵² and p²⁷ antigens to determine the presence of endogenous MMTV gene activity. Only occasional C3H/StWi tumors were positive and in most of these, p²⁷, but not gp⁵² was detected, suggesting non-coordinate expression of these endogenous MMTV gene products. Both alveolar (HAN) and ductal hyperplasia (DH) were found in DMBA-treated C3H/StMTV glands, whereas only DH were found in DMBA-treated C3H/StWi mice. Nevertheless, the DMBA-induced C3H/StMTV tumor histopathology was remarkably indistinguishable from that in tumors produced by DMBA in C3H/StWi mice, implying that in both groups, tumors arose primarily from the chemically-induced mammary dysplasias. These data taken together appear to support the conclusion that DMBA and Mmtv follow separate pathways to the induction of cancer in the mouse mammary gland.