Chemical-retroviral cooperative carcinogenesis and its molecular basis in NIH/3T3 cells.
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.
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Y
Y
Hassan
E
E
Priel
S
S
Segal
M
M
Huleihel
M
M
Aboud
D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003043:Cocarcinogenesis; D015342:DNA Probes; D004586:Electrophoresis; D005786:Gene Expression Regulation; D016259:Genes, myc; D011905:Genes, ras; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D007942:Leukemia, Experimental / Q000209:etiology*; D008748:Methylcholanthrene / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000472:pathogenicity*; D009693:Nucleic Acid Hybridization; D011061:Poly A / Q000032:analysis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase / Q000032:analysis
D015342:DNA Probes; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D011061:Poly A; D008748:Methylcholanthrene; D012313:RNA; D012194:RNA-Directed DNA Polymerase