HOST-RANGE RESTRICTIONS OF ONCOGENES - MYC GENES TRANSFORM AVIAN BUT NOT MAMMALIAN-CELLS AND MHT RAF GENES TRANSFORM MAMMALIAN BUT NOT AVIAN CELLS/

The host range of retroviral oncogenes is naturally limited by the hos t range of the retroviral vector, The question of whether the transfor ming host range of retroviral oncogenes is also restricted by the host species has not been directly addressed, Here we have tested in avian and murine host species the transforming host range of two retroviral one genes, myc of avian carcinoma viruses MH2 and MC29 and mht/raf of avian carcinoma virus MH2 and murine sarcoma virus MSV 3611, Virus ve ctor-mediated host restriction was bypassed by recombining viral oncog enes with retroviral vectors that can readily infect the host to be te sted, It,vas found that, despite high expression, transforming functio n of retroviral myc genes is restricted to avian cells, and that of re troviral mht/raf genes is restricted to murine cells, Since retroviral oncogenes encode the same proteins as certain cellular genes, termed protooncogenes, our data must also be relevant to the oncogene hypothe sis of cancer, According to this hypothesis, cancer is caused by mutat ion of protooncogenes, Because protooncogenes are conserved in evoluti on and are presumed to have conserved functions, the oncogene hypothes is assumes no host range restriction of transforming function, For exa mple, mutated human proto-myc is postulated to cause Burkitt lymphoma, because avian retroviruses with myc genes cause cancer in birds, But there is no evidence that known mutated protooncogenes can transform h uman cells, The findings reported here indicate that host range restri ction appears to be one of the reasons (in addition to insufficient tr anscriptional activation) why known, mutated protooncogenes lack trans forming function in human cells.