Inhibition of malignant transformation in vitro by inhibitors of poly(ADP-ribose) synthesis.
- 1 January 1984
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 81 (1) , 243-247
- https://doi.org/10.1073/pnas.81.1.243
Abstract
Malignant transformation in vitro of hamster embryo cells and mouse [embryo fibroblast] C3H 10T1/2 cells by X-rays, UV 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 UV 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. Mechanisms regulating malignant transformation are probably 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.Keywords
This publication has 29 references indexed in Scilit:
- Hypomethylation of ras oncogenes in primary human cancersPublished by Elsevier ,2005
- Hypomethylation distinguishes genes of some human cancers from their normal counterpartsNature, 1983
- Abnormal NAD+ levels in cells from patients with Fanconi's anaemiaNature, 1982
- 3-Aminobenzamide synergistically increases sister-chromatid exchanges in cells exposed to methyl methanesulfonate but not to ultraviolet lightMutation Research Letters, 1982
- Ultraviolet hypersensitivity of Cockayne's syndrome fibroblastsExperimental Cell Research, 1982
- High incidence of sister chromatid exchanges and chromatid interchanges in the conditions of lowered activity of poly(ADP-ribose)polymeraseBiochemical and Biophysical Research Communications, 1981
- Protease inhibitors neither damage DNA nor interfere with DNA repair or replication in human cellsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1981
- Mutagenesis and transformation of normal cells by chemical carcinogensNature, 1976
- Excision repair (dimer excision, strand breakage and repair replication) in primary cultures of eukaryotic (bovine) cellsExperimental Cell Research, 1972
- In Vitro Cell Transformation by X-IrradiationNature, 1966