Mouse-strain difference in immunoprophylactic and immunotherapeutic effects of BCG on carcinogen-induced autochthonous tumors

Abstract

The prophylactic and therapeutic effects of BCG on the tumors induced by 3-methylcholanthrene (MCA) were studied comparatively between two inbred mouse strains, SWM/Ms and C3H/He, the first tumor appeared 5 weeks after MCA and the cumulative tumor incidence reached almost 100% within 20 weeks. On the other hand, the first tumor appeared 8 weeks after MCA in SWM/Ms, the number of tumor-bearers increased more slowly than in C3H/He, and the final tumor incidence (at 30 weeks) was about 90-80%. Single subcutaneous injection with BCG 2 weeks prior to MCA significantly protected SWM/Ms from tumor development, but not in C3H/He. These tumors, once appeared grew progressively and killed the hosts equally in both the strains. Intratumor (i.t.) injection with BCG showed more or less therapeutic effects in SWM/Ms; most tumors regressed or retarded after BCG. The time period after tumor-appearance to tumor-death was prolonged in most of SWM/Ms mice given i.t. injection with BCG, except a few mice that died earlier than non-treated controls after BCG. Contrary, no therapeutic effect of i.t. injection with BCG was observed in C3H/He. different host responses to BCG between SWM/Ms and C3H/He were found by the peritoneal macrophage disappearance test and the footpad reaction test; SWM/Ms was a high-responder to BCG and C3H/He was a low-responder. The marked differences between SWM/Ms and C3H/He in prophylactic and therapeutic effects of BCG on the autochthonous tumors were discussed in terms of difference of the host immune response to BCG that is defined genetically.