Relationship between DNA strand breaks and inhibition of poly (ADP-ribosylation): enhancement of carcinogen-induced transformation.
Inhibition of poly(ADP-Rib) by benzamide (BA) or 3-amino-benzamide (3AB) for a limited period (i.e., when ADP-ribosylation is elevated) during and shortly following X-ray or MNNG-induced DNA damage of BALB/3T3 cells significantly (3- to 30-fold) enhanced transformation frequency by these agents. Individual Type III foci isolated from benzamide, X-ray, or X-ray plus benzamide treated cultures were established and characterized for growth in soft agar and for tumor induction in nude mice. DNA isolated from representative transformed lines established as a result of BA, X-ray or X-ray and BA treatments was transfected onto NIH/3T3 cells. Transformation efficiencies ranging from 0.17 to 0.28 foci/micrograms of DNA were observed suggesting the possibility that dominant transforming gene(s) were responsible for the oncogenic phenotype of radiation and benzamide transformed DNA.
Kasid
U N
UN
Stefanik
D F
DF
Lubet
R A
RA
Dritschilo
A
A
Smulson
M E
ME
D000818:Animals; D001483:Base Sequence; D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000032:analysis; D008769:Methylnitronitrosoguanidine; D051379:Mice; D009243:NAD / Q000378:metabolism; D009857:Oncogenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D001549:Benzamides; D004273:DNA, Neoplasm; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D008769:Methylnitronitrosoguanidine; C037689:benzamide; C025160:3-aminobenzamide; D004247:DNA