Chemical‐viral co‐carcinogenesis: Requirement for leukemia virus expression in accelerated transformation

Abstract

The essential role of Rauscher leukemia virus (RLV) multiplication in viral-chemical co-carcinogenesis was investigated by the use of ethidium bromide (EtBr) as an inhibitor of viral complementary DNA (cDNA) integration in the host genome. EtBr inhibited co-carcinogenic transformation when present at the time of RLV inoculation but was ineffective when added to preinfected cells. Inhibitors of protein synthesis, puromycin and cyclohexamide also inhibited co-carcinogenic transformation of chronically infected cells. Purified rat interferon used at a concentration which inhibited 85% of RLV production did not modify the course of co-carcinogenic transformation. The implications of these observations in terms of the possible role of the virus-specific protein (s) in the co-carcinogenic process are discussed.

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

“…However, IFN is completely ineffective in this respect when added with the carcinogen after a high number of passages p.i. Similar results have been reported by Mishra et al (1976) with ethidium bromide or antiviral antibody; the former blocks provirus integration (Guntaka et al, 1975), whereas the latter exerts its effect probably by preventing superinfections. Nevertheless, we cannot exclude the possibility that provirus accumulation might be mediated by reverse transcription of endogenous viral RNA into viral DNA independently of exogenous superinfection, as shown in some cases (Varmus & Shank, 1976;Shen-Ong & Cole, 1984), or by transposition (Heidman et al, 1988) and other amplification mechanisms (Dudley & Risser, 1984;Colombo et al, 1988).…”

Potentiating Effect of Methyl Methane Sulfonate on Friend Virus Leukemogenesis in Vivo

“…Ball and McCarter (3) and Igel et al (4) subsequently demonstrated reproducible activation and production of leukemia virus after treatment with chemical carcinogens. These findings have been confirmed in a number of in vivo and in vitro studies suggesting that interaction with exogenous (5)(6)(7)(8)(9)(10)(11)(12) or endogenous (13)(14)(15)(16) viruses may play an important role in the production of some tumors by chemical carcinogens (also see 17 for review). More recently, Pottathil ef al.…”

“…Previous studies have shown that in certain systems potentially oncogenic viruses could be activated by exposure to chemical carcinogens in vivo (3, 4, 6, 13-16, 32, 33), or could interact with chemical carcinogens in vitro (5)(6)(7)(8)(9)(10)(11)(12). The purpose of the present studies was to examine in vivo some of the conditions under which interactions may occur and to determine if given in common the two agents might produce cancer in animals otherwise resistant to induction of the disease.…”

“…To explain these observations, effects of chemical carcinogens on both the immune response (19) and the transforming target cell itself (5,8) have been postulated. Even in vitro the mechanism by which chemicals potentiate the carcinogenic action of viruses remains uncertain, although all of the chemical agents thus far found to be active in this way have been shown to interact with DNA (20).…”

Studies on the mechanism of 1,3-butadiene-induced leukemogenesis: the potential role of endogenous murine leukemia virus.

“…Although the data are incompatible with the hypothesis that leukemogenic MuLV are entirely responsible for the incidence of thymic lymphoma, the described studies suggest that ecotropic MuLV may influence the incidence of 1,3-butadiene-induced lymphoma in the mouse. A major difference between NIH Swiss and B6C3F1 mice is their respective ecotropic retroviral background, and the prospect that differences in leukemia incidence could be explained by strain-specific metabolism or bioactivation of 1,3-butadiene remains unlikely, since, with the exception of the increased recovery of ecotropic retrovirus from tissues of B6C3F1 mice, target organ toxicity in the two strains is qualitatively and quantitatively identical (34)(35)(36)(37)(38).…”