Relationship between DNA strand breaks and inhibition of poly(ADP-ribosylation): enhancement of carcinogen-induced transformation |
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| Authors: | Kasid, Usha N. Stefanik, David F. Lubet, Ronald A. Dritschilo, Anatoly Smulson, Mark E. |
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| Affiliation: | Department of Biochemistry and Radiation Medicine, Georgsetown University School of Medicine and The Vincent T.Lombardi Cancer Research Center Washington, DC 20007
1Department of Genetic Toxicology, Microbiological Associates 5221 River Road, Bethesda, MD 20816, USA |
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| Abstract: | Inhibition of poly(ADP-Rib) by benzamide (BA) or 3-aminobenzamide(3AB) for a limited period (i.e., when ADP-ribosylation is elevated)during and shortly following X-ray or MNNG-induced DNA damageof BALB/3T3 cells significantly (3- to 30-fold) enhanced transformationfrequency by these agents. Individual Type III foci isolatedfrom benzamide, X-ray, or X-ray plus benzamide treated cultureswere established and characterized for growth in soft agar andfor tumor induction in nude mice. DNA isolated from representativetransformed lines established as a result of BA, X-ray or X-rayand BA treatments was transfected onto NIH/3T3 cells. Transformationefficiencies ranging from 0.17 to 0.28 foci/ µg of DNAwere observed suggesting the possibility that dominant transforminggene(s) were responsible for the oncogenic phenotype of radiationand benzamide transformed DNA. |
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