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Inhibition of carcinogen‐induced cellular transformation of human fibroblasts by drugs that interact with the poly(ADP‐ribose) polymerase system
Author(s) -
Milo George E.,
Kurian Ponnama,
Kirsten Eva,
Kun Ernest
Publication year - 1985
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(85)80546-9
Subject(s) - poly adp ribose polymerase , polymerase , transformation (genetics) , carcinogen , chemistry , ribose , biochemistry , microbiology and biotechnology , cancer research , dna , biology , enzyme , gene
Two types of interactions of 13 drugs with human fibroblasts were determined: (a) I 50 of nuclear poly(ADP‐ribose) polymerase, as assayed with isolated nuclei in vitro, and (b) the non‐toxic concentration of drugs that prevented carcinogen‐induced cell transformation of intact fibroblasts (RCF 1 ). In general, RCF 1 was much lower than I 50 , and one antitransformer did not inhibit the enzyme in vitro, indicating that low‐affinity enzyme inhibitory sites appear to play no role in the mechanism of prevention of cell transformation. Two enzyme inhibitors, caffeine and 1‐methylnicotinamide, exhibited no antitransforming activity. Benzamide when applied in population doubling 1 induced resistance to cell transformation in population doubling 6 by carcinogens added at this stage.

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