Effects of exposure protocols on induction of kinetochore-plus and -minus micronuclei by arsenite in diploid human fibroblasts.
Arsenic, widely distributed in the environment, is a potent human carcinogen. Arsenite genotoxicity has been observed in a variety of cells and animal systems. However, the underlying mechanism is not completely clear. In this study, human fibroblasts (HFW) were treated with 1.25-10 microM arsenite for 24 h (low dose and long exposure) and 5-80 microM for 4 h (high dose and short exposure), and the arsenite accumulation, cytotoxicity, and micronucleus (MN) induction were examined. By these two different protocols, HFW cells showed equivalent levels of arsenite accumulation, but exhibited different kinetics of cell killing and different types of MN generation. Arsenite induced mainly kinetochore-positive MN (K+-MN) in HFW cells by low dose exposure whereas mainly kinetochore-negative MN (K--MN) was induced by high dose exposure. Catalase reduced both K+- and K--MN induced by these two exposure protocols. Except for the case of K+-MN induction by the high dose exposure protocol, N-acetyl-cysteine (NAC) in both low and high dose protocols was also shown to effectively reduce arsenite-induced MN. The present results imply that oxidative stress is involved in arsenite-induced MN in diploid human fibroblasts. However, different protocols for arsenite exposure may result in different cellular damage.
Yih
L H
LH
Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
Lee
T C
TC
D000111:Acetylcysteine / Q000494:pharmacology; D018053:Arsenites / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000187:drug effects*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D018384:Oxidative Stress; D017670:Sodium Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*
D018053:Arsenites; D002273:Carcinogens; D017670:Sodium Compounds; C017947:sodium arsenite; D002374:Catalase; D000111:Acetylcysteine