Effects of ICRF-193, a catalytic inhibitor of DNA topoisomerase II, on sister chromatid exchange.
To investigate whether mammalian DNA topoisomerase II is directly involved in recombination events, the effects of ICRF-193, a specific catalytic inhibitor on sister chromatid exchange (SCE), were examined in MR-6 cells. ICRF-193 only slightly elevated SCE formation after 3 or 44 h treatments, while VP-16, a cleavable complex forming type of topoisomerase II inhibitor, caused significant enhancement. ICRF-193 had no effect on N-methyl-N'-nitro-N-nitrosoguanidine-induced SCE formation. It would thus appear that the inhibition of topoisomerase II does not affect recombinational repair, and that topoisomerase II inhibitors such as VP-16 and 4'-(9-acridinyl amino) methane sulfon-m-anisidide induce SCE through production of DNA strand breaks, rather than by inhibiting the enzyme activity.
Hamatake
M
M
Department of Pharmacy, Aichi Cancer Research Hospital, Nagoya, Japan.
Andoh
T
T
Ishida
R
R
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D054659:Diketopiperazines; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D054659:Diketopiperazines; D004791:Enzyme Inhibitors; D009153:Mutagens; D010879:Piperazines; D059005:Topoisomerase II Inhibitors; D008769:Methylnitronitrosoguanidine; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione; D005047:Etoposide