Document Detail


Evidence for reactive oxygen species inducing mutations in mammalian cells.
MedLine Citation:
PMID:  2432598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A W Hsie; L Recio; D S Katz; C Q Lee; M Wagner; R L Schenley
Related Documents :
9554828 - Phagomimetic action of antimicrobial agents.
10401598 - H2o2 mediates o2 toxicity in cultured fetal rat distal lung epithelial cells.
2858098 - Oxygen chemoreception by carotid body cells in culture.
20025968 - Cytotoxicity study of ordered mesoporous silica mcm-41 and sba-15 microparticles on cac...
22590558 - A real time metridia luciferase based non-invasive reporter assay of mammalian cell via...
20079458 - Oxidative damage induced by carcinogenic polycyclic aromatic hydrocarbons and organic e...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
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:
Created Date:  1987-02-06     Completed Date:  1987-02-06     Revised Date:  2010-09-09    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9616-20     Citation Subset:  IM; S    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
CA09336/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Allelic variation in human mitochondrial genes based on patterns of restriction site polymorphism.
Next Document:  Restricted neutralization of divergent human T-lymphotropic virus type III isolates by antibodies to...