摘要
To investigate the role of topoisomerases in the production of sister chromatid exchanges, the effects of inhibitors of type I and II topoisomerases on baseline and mutagen-induced sister chromatid exchanges were compared. V79 cells were treated with VM-26 and m-AMSA, known inhibitors of type II topoisomerase, or with camptothecin, the only known inhibitor of type I topoisomerase. We observed that inhibitors of both type I and II topoisomerases induced high levels of sister chromatid exchanges at 10-6 M, and that the dose-response curves of these drugs were very similar. A clear heterogeneity in the distribution patterns of exchanges induced by inhibitors of topoisomerases was observed. We believe that this heterogeneity in response to these compounds is due to variation in sensitivity within the cell cycle. We also studied interactions of these agents with mitomycin-C and with PUVA (8-methoxypsoralen + UVA), both cross-linking agents and potent sister chromatid exchange inducers, and with x-rays, an agent that induces high levels of DNA strand breaks. No significant change in exchange levels was observed in interactions between topoisomerase inhibition and the levels induced by the agents studied. We conclude that double-strand break prevalence, known to be increased through inhibition of type II topoisomerase, is not the primary mechanism for induction of sister chromatid exchanges. We further conclude that acute inhibition of type I and type II topoisomerases does not influence substantially the induction of exchanges by other agents.
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 485-494 |
| 頁數 | 10 |
| 期刊 | Cell Biology and Toxicology |
| 卷 | 2 |
| 發行號 | 4 |
| DOIs | |
| 出版狀態 | 已發佈 - 十二月 1986 |
| 對外發佈 | Yes |
指紋
ASJC Scopus subject areas
- Toxicology
- Cell Biology
引用此文
Induction of sister chromatid exchanges by inhibitors of topoisomerases. / Lim, Meesun; Liu, Leroy-Fong; Jacobson-Kram, David; Williams, Jerry R.
於: Cell Biology and Toxicology, 卷 2, 編號 4, 12.1986, p. 485-494.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - Induction of sister chromatid exchanges by inhibitors of topoisomerases
AU - Lim, Meesun
AU - Liu, Leroy-Fong
AU - Jacobson-Kram, David
AU - Williams, Jerry R.
PY - 1986/12
Y1 - 1986/12
N2 - To investigate the role of topoisomerases in the production of sister chromatid exchanges, the effects of inhibitors of type I and II topoisomerases on baseline and mutagen-induced sister chromatid exchanges were compared. V79 cells were treated with VM-26 and m-AMSA, known inhibitors of type II topoisomerase, or with camptothecin, the only known inhibitor of type I topoisomerase. We observed that inhibitors of both type I and II topoisomerases induced high levels of sister chromatid exchanges at 10-6 M, and that the dose-response curves of these drugs were very similar. A clear heterogeneity in the distribution patterns of exchanges induced by inhibitors of topoisomerases was observed. We believe that this heterogeneity in response to these compounds is due to variation in sensitivity within the cell cycle. We also studied interactions of these agents with mitomycin-C and with PUVA (8-methoxypsoralen + UVA), both cross-linking agents and potent sister chromatid exchange inducers, and with x-rays, an agent that induces high levels of DNA strand breaks. No significant change in exchange levels was observed in interactions between topoisomerase inhibition and the levels induced by the agents studied. We conclude that double-strand break prevalence, known to be increased through inhibition of type II topoisomerase, is not the primary mechanism for induction of sister chromatid exchanges. We further conclude that acute inhibition of type I and type II topoisomerases does not influence substantially the induction of exchanges by other agents.
AB - To investigate the role of topoisomerases in the production of sister chromatid exchanges, the effects of inhibitors of type I and II topoisomerases on baseline and mutagen-induced sister chromatid exchanges were compared. V79 cells were treated with VM-26 and m-AMSA, known inhibitors of type II topoisomerase, or with camptothecin, the only known inhibitor of type I topoisomerase. We observed that inhibitors of both type I and II topoisomerases induced high levels of sister chromatid exchanges at 10-6 M, and that the dose-response curves of these drugs were very similar. A clear heterogeneity in the distribution patterns of exchanges induced by inhibitors of topoisomerases was observed. We believe that this heterogeneity in response to these compounds is due to variation in sensitivity within the cell cycle. We also studied interactions of these agents with mitomycin-C and with PUVA (8-methoxypsoralen + UVA), both cross-linking agents and potent sister chromatid exchange inducers, and with x-rays, an agent that induces high levels of DNA strand breaks. No significant change in exchange levels was observed in interactions between topoisomerase inhibition and the levels induced by the agents studied. We conclude that double-strand break prevalence, known to be increased through inhibition of type II topoisomerase, is not the primary mechanism for induction of sister chromatid exchanges. We further conclude that acute inhibition of type I and type II topoisomerases does not influence substantially the induction of exchanges by other agents.
KW - camptothecin
KW - m-AMSA
KW - sister chromatid exchange
KW - topoisomerase
KW - VM-26
UR - http://www.scopus.com/inward/record.url?scp=0023006294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023006294&partnerID=8YFLogxK
U2 - 10.1007/BF00117850
DO - 10.1007/BF00117850
M3 - Article
C2 - 2855799
AN - SCOPUS:0023006294
VL - 2
SP - 485
EP - 494
JO - Cell Biology and Toxicology
JF - Cell Biology and Toxicology
SN - 0742-2091
IS - 4
ER -