| Evidence for reactive oxygen species inducing mutations in mammalian cells. | |
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MedLine Citation:
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PMID: 2432598 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have studied the mutagenicity (by selecting for mutants resistant to 6-thioguanine) and cytotoxicity (by determining cellular cloning efficiency) of physical and chemical agents in Chinese hamster ovary (CHO) cells, clone CHO-K1-BH4 (K1-BH4), and its radiation-hypersensitive transformant, AS52. AS52 cells contain a single functional copy of a bacterial gene, the xanthine/guanine phosphoribosyltransferase (gpt) gene instead of its mammalian equivalent, the hypoxanthine/guanine phosphoribosyltransferase (hprt) gene. We found that x-ray and neutron irradiations are equally toxic to both cell types; however, these physical agents are approximately equal to 10 times more mutagenic to AS52 cells than to K1-BH4 cells. Our earlier studies using Southern blot analysis showed that x-irradiation produces mostly or exclusively deletion mutations in both cell types. If reactive oxygen species mediate the mutagenic effects of radiations and chemicals, then radiomimetic compounds such as streptonigrin and bleomycin, which exert their biological effects via reactive oxygen species, and oxidizing compounds such as potassium superoxide and hydrogen peroxide should elicit a similar differential mutagenic response in both cell types. On the other hand, agents such as ethyl methanesulfonate, ICR 191, and UV light, which do not produce reactive oxygen species, should not elicit differential mutagenicity. Our results fulfill such predictions. The apparent hypermutability of AS52 cells probably results from a higher recovery of multilocus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced mutants. |
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Authors:
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A W Hsie; L Recio; D S Katz; C Q Lee; M Wagner; R L Schenley |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 83 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 1986 Dec |
Date Detail:
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Created Date: 1987-02-06 Completed Date: 1987-02-06 Revised Date: 2010-09-09 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 9616-20 Citation Subset: IM; S |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bleomycin / toxicity Cell Line Cell Survival / drug effects, radiation effects Cricetinae DNA / drug effects, radiation effects DNA Damage Free Radicals Hydrogen Peroxide / toxicity Mutation / drug effects* Neutrons Oxygen / toxicity* Streptonigrin / toxicity Superoxides / toxicity X-Rays |
| Grant Support | |
ID/Acronym/Agency:
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CA09336/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Free Radicals; 11056-06-7/Bleomycin; 11062-77-4/Superoxides; 3930-19-6/Streptonigrin; 7722-84-1/Hydrogen Peroxide; 7782-44-7/Oxygen; 9007-49-2/DNA |
| Comments/Corrections | |
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