Biomedical subjects
Publications and source records attributed to M Calvin.
A reverse transcriptase activity, extracted from virus-transformed cells, is activated by very low concentrations of nonionic detergents. These same detergents also significantly reduce the effectiveness of certain rifamycin derivatives as inhibitors of the polymerase activity when the detergents are present at micelle-forming concentrations.
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One of the most potent inhibitors of RNA-dependent DNA polymerase activity so far described (rifazacyclo-16) was not correspondingly as active in focus inhibition. This discrepancy was thought to be due to the inability of the drug to penetrate the cell membrane. It has been found that a very low level of amphotericin B allows this drug, as well as the previously described 2',6'-dimethyl-N(4')benzyl-N(4')-[desmethyl] rifampicin, to exhibit a very high capability to inhibit focus formation. Since these two drugs are highly lipophilie, their activity may be expected to be dependent upon any lipophilic components in the medium, such as serum or detergents. The use of amphotericin B as well as serum in tissue cultures is common, and could account for some of the variability in focus inhibition reported in the literature.
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The chemical reactivity and presumably the carcinogenic activity induced in aromatic hydrocarbons by hydroxylating enzymes may be due to the generation of electrophilic centers in some (benzo[a]pyrene) or nucleophilic centers in others (7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene). These centers, which are at positions complementary to the points of activation by acid-derived protons (models of the positive oxygen of the hydroxylating enzymes), may react simultaneously with corresponding cellular components.
It is shown that rifampicin, and especially the related antibiotic 2',6'-dimethyl-N(4')-benzyl-N(4')- [desmethyl]rifampicin (DMB-rifampicin) can inhibit focus formation by Moloney sarcoma virus on BALB/3T3 tissue cultures. At 10 mug/ml DMB-rifampicin totally inhibits focus formation while reducing virus replication by at least a factor of fifty and cell proliferation by only a factor of three. These observations, taken together with those of others, suggest a role for an RNA-dependent DNA polymerase and the gene for its synthesis both in normal cell processes and in the transformation process.
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