Open AccessInhibition of malignant transformation in vitro by inhibitors of poly(ADP-ribose) synthesis.
Author(s) -
Carmia Borek,
William F. Morgan,
Augustinus Ong,
James E. Cleaver
Publication year - 1984
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.81.1.243
Subject(s) - mutagenesis , dna repair , ultraviolet light , sister chromatid exchange , dna , dna damage , biochemistry , sister chromatids , biology , postreplication repair , hamster , microbiology and biotechnology , transformation (genetics) , dna synthesis , chemistry , mutation , nucleotide excision repair , gene , photochemistry , chromosome
Malignant transformation in vitro of hamster embryo cells and mouse C3H 10T 1/2 cells by x-rays, ultraviolet light, and chemical carcinogens was inhibited by benzamide and by 3-aminobenzamide at concentrations that are specific for inhibition of poly(ADP-ribose) formation. These compounds slow the ligation stage of repair of x-ray and alkylation damage but not of ultraviolet light damage. At high concentrations they also inhibited de novo synthesis of DNA purines and DNA methylation by S-adenosylmethionine. The suppression of transformation by the benzamides is in striking contrast to their reported effectiveness in enhancing sister chromatid exchange, mutagenesis, and killing in cells exposed to alkylating agents. Our results suggest that mechanisms regulating malignant transformation are different from those regulating DNA repair, sister chromatid exchange, and mutagenesis and may be associated with changes in gene regulation and expression caused by alterations in poly(ADP-ribosyl)ation.