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THE EFFECTS OF HEAT SHOCK PROTEIN 70 (HSP70) AND EXPOSURE PROTOCOL ON ARSENITE INDUCED GENOTOXICITY
Citation:
Barnes, J A., B W. Collins, D J. Dix, AND J W. Allen. THE EFFECTS OF HEAT SHOCK PROTEIN 70 (HSP70) AND EXPOSURE PROTOCOL ON ARSENITE INDUCED GENOTOXICITY. TOXICOLOGY AND APPLIED PHARMACOLOGY 40(4):236-242, (2002).
Description:
The Effects of Heat Shock Protein 70 (Hsp70) and Exposure Protocol on Arsenite Induced Genotoxicity
Barnes, J.A.1,2, Collins, B.W.2, Dix, D.J.3 and Allen J.W2.
1National Research Council, 2Environmental Carcinogenesis Division, 3Reproductive Toxicology Division, Office of Research and Development, U.S. Environmental Protection Agency, RTP, NC
Abstract
Arsenic (As), a human carcinogen, is known to be genotoxic although it?s mechanism(s) of action involved in tumorigenesis are not well understood. Among the toxicity-related properties of interest for this chemical are it?s clastogenic and aneugenic activities, as well as it?s capacity for inducing stress-response in the form of elevated heat shock protein (Hsp) expression. In the present study, we have evaluated the effects of alternative arsenic exposure protocols and elevated cellular Hsp70 expression on the production of structural and numerical types of chromosome anomalies. Following different in vitro sodium arsenite treatments of MCF-7 human breast cancer cells with tetracycline regulation of Hsp70 expression levels, a cytokinesis block micronucleus assay with kinetochore immunostaining was used to detect micronuclei derived from chromosome breakage (K-) or loss (K+). These studies demonstrated significant increases in micronucleus frequencies following either a low dose long exposure (5 or 10 mM for 46 hrs), or a high dose short exposure (10 or 40 mM for 8 hrs), to sodium arsenite. Overall, low dose long exposures were more efficient in producing K+ MN and cells with multiple MN. With either the long or short exposure protocol, cells expressing elevated Hsp70 revealed significantly lower levels of arsenic induced MN of both K+ and K- types. We conclude that the dose and duration of arsenite exposure influence the type, as well as amount of chromosome damage produced, and that inducible Hsp70 has a discernible protective effect against both clastogenic and aneugenic forms of this damage.
Key Words
Arsenic, Hsp70, DNA damage, micronuclei