Chemical-retroviral cooperative carcinogenesis and its molecular basis in NIH/3T3 cells

Abstract

We demonstrate in this study that infection with Moloney murine leukemia virus (M-MLV) and exposure to 3-methylcholanthrene (3-MC) can cooperate to transform NIH/3T3 mouse fibroblasts. M-MLV seems to stimulate the expression of c-myc and of a certain major histocompatibility complex (MHC) class I gene. Yet M-MLV infection by itself is insufficient to transform these cells. However, exposure of the infected cells to 3-MC resulted in a rapid cell transformation with concomitant enhancement of c-Ha-ras and H-2K class I MHC gene expression in the transformed cells. No such transformation was observed when uninfected NIH/3T3 cells were similarly treated with this carcinogen. Clones of cells transformed by this combined effect of M-MLV and 3-MC were found to be highly tumorigenic in fully immunocompetent allogeneic BALB/c mice. We provide evidence to suggest that the enhanced expression of the H-2K gene in these transformed cells plays an important role in overcoming the BALB/c allogeneic barrier and allowing tumor growth in these mice.

A transcript from the long terminal repeats of a murine retrovirus associated with trans activation of cellular genes

“…A number of studies have demonstrated an increase in major histocompatibility complex (MHC) antigen expression on cells infected in vitro (14,15,18) or in vivo (6,19,26) with leukemogenic murine and human retroviruses (see reference 13 for a review). We have previously documented that stable or transient infection of murine or human fibroblast or lymphoid cells by Moloney murine leukemia virus (M-MuLV) results in an elevation (by up to 70-fold) of a number of cell surface antigens, including CD2, CD3, CD4, class I MHC, and TcR␤, and comparable increases in their respective transcripts.…”

Amplification of the Moloney murine leukaemia virus genome and its possible role in facilitation of chemical carcinogenesis in normal rat kidney cells

“…Exogenous as well as activated endogenous non-transforming retroviruses have heen shown in numerous early studies (reviewed by Tennant & Rascatti, 1980) and more recently by our laboratory (Hassan et al, 1985(Hassan et al, , 1986(Hassan et al, , 1990 to facilitate chemical carcinogenesis in mouse and rat cells. To investigate whether a single active provirus is sufficient to exert this synergistic effect, we have generated a cell clone from a single normal rat kidney (NRK) cell infected with a single infectious particle of Moloney murine leukaemia virus (M-MLV) and found that, unlike the uninfected parental NRK cells which are highly resistant to chemical carcinogenesis, this clone (NRK/MLV) can indeed be transformed by 3-methylcholanthrene (3-MC).…”