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Activation of carcinogenic polycyclic hydrocarbons in polyoma-virus-transformed cells as a prerequisite for polyoma virus induction

✍ Scribed by Eliezer Huberman; Marian Fogel


Publisher
John Wiley and Sons
Year
1975
Tongue
French
Weight
509 KB
Volume
15
Category
Article
ISSN
0020-7136

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✦ Synopsis


Abstract

Polyoma‐virus (PV)‐transformed cell clones, which are inducible for virus synthesis by various physical and chemical agents, metabolize the chemically non‐reactive carcinogen benzo (a)pyrene (BP) into water‐soluble products. In cultures of such clones, which metabolize BP to a level of 30–60% of that of normal cells, up to 10.4% of the cells were induced for PV synthesis by BP, 20‐methylcholanthrene (MCA) and 7,12‐dimethylbenz (a) anthracene (DMBA). No PV induction was observed with the non‐carcinogenic polycyclic hydrocarbons pyrene chrysene and benz (a)‐anthracene. A proportion of subclones, isolated from a PV‐inducible clone, which metabolized 0.1 μg or less BP per 10^6^ cells, proved non‐inducible by any of the carcinogenic polycyclic hydrocarbons BP, MCA and DMBA. However, subclones which metabolized more than 0.3 μg BP per 10^6^ cells were all inducible for PV synthesis by these carcinogens. Subclones isolated from an inducible clone pretreated with BP were shown to metabolize less than 0.1 μg BP per 10^6^ cells and were resistant to virus induction by the carcinogenic polycyclic hydrocarbons. Benzoflavone, which inhibited the metabolism of BP in clones metabolizing high levels of this carcinogen, also prevented the induction of PV antigen and infectious virus synthesis in these clones. The data indicate a relationship between the carcinogenicity of polycyclic hydrocarbons and their ability to induce virus in the PV‐transformed cells and suggest that virus induction depends on metabolic conversion of these hydrocarbons into similar reactive compounds that are responsible for malignant transformation and mutagenesis.


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