Abnormal sister-chromatid exchange induction by 3-aminobenzamide in an SV40-transformed Indian muntjac cell line: relationships with DNA maturation and DNA-strand breakage.
In SVM cells, an SV40-transformed line of Indian muntjac fibroblasts, levels of sister-chromatid exchanges are known to be abnormally high after UV-irradiation or alkylation. The SVM line is also known to have a defect in the processing of DNA-strand breaks. Sister-chromatid exchange in other cells is known to be stimulated by the poly(ADP-ribose) transferase inhibitor, 3-aminobenzamide, which also retards DNA-break sealing. Sister-chromatid exchanges in SVM cells are found to be hypersensitive to 3-aminobenzamide, or to nicotinamide deprivation which similarly inhibits poly(ADP-ribosyl)ation; DNA-strand breaks are likewise induced by 3-aminobenzamide. Bromodeoxyuridine, needed to detect sister-chromatid exchanges, is more toxic to SVM cells and itself induces sister-chromatid exchanges to a greater extent than it does in normal muntjac cells. However, in contrast to the situation reported for other cell types prone to sister-chromatid exchange (the Chinese hamster ovary mutant EM9 and human Bloom's Syndrome cells), SVM cells do not show an abnormal delay in DNA maturation when, under the influence of bromodeoxyuridine and 3-aminobenzamide, they show a high level of sister-chromatid exchange. The mechanism by which BrdU exerts its effects can largely be explained in terms of familiar effects on deoxyribonucleotide pools and DNA integrity. 3-Aminobenzamide, however, induces sister-chromatid exchanges in SVM cells by another mechanism.
Jha
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Department of Zoology, Cambridge University, Great Britain.
Bouffler
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Downes
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CS
Johnson
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RT
D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D001973:Bromodeoxyuridine / Q000633:toxicity; D002461:Cell Line, Transformed; D002470:Cell Survival; D004249:DNA Damage; D004261:DNA Replication; D003670:Deer; D005347:Fibroblasts; D007700:Kinetics; D009536:Niacinamide / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013539:Simian virus 40; D012854:Sister Chromatid Exchange
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; C025160:3-aminobenzamide; D001973:Bromodeoxyuridine