DEVELOPMENT OF MAMMARY TUMOR AND THE ROLE OF ENDOGENOUS MAMMARY TUMOR VIRUS IN MICE

Occurrence of spontaneous tumor in experimental animals is of great concern in long-term carcinogenic and chronic toxicity studies. Among spontaneous tumors, mammary tumor is one of the most predominant tumor in mice. However, it is well known that mouse mammary tumor virus (MMTV) is widely involved in all cells in the mice in a proviral form. Based on endogenous viral gene patterns, all strains of mice including inbred or non-inbred carried 2-6 such genes, though the incidence of mammary tumor is different depending on the strains. Administration of urethane in the drinking water of breeding mice lead to a higher incidence of mammary tumor at an early age in these strains. Urethane, however, did not induce or enhance endogenous retroviral antigen expression or increase in MMTV-DNA sequences in mammary tumor by radioimmunoassay or molecular hybridization. These results showed that MMTV was not involved in chemical carcinogenesis of the mouse mammary glands. In regard to mammary tumors in carcinogenic or chronic toxicity studies, we must examine further whether endogenous MMTV is activated or not.