XRCC1 protects cells from chromate-induced chromosome damage, but does not affect cytotoxicity.
Hexavalent chromium Cr(VI) is a well known human carcinogen. This genotoxic metal induces DNA strand breaks and chromosome damage. However, the relationship between these lesions is uncertain. Our study focused on examining the role of XRCC1 in sodium chromate-induced cytotoxicity and chromosomal aberrations in Chinese Hamster Ovary (CHO) cells. Three different cell lines were used: AA8 (parental), EM9 (XRCC1 mutant) and H9T3 (EM9 complemented with human XRCC1 gene). Results show that concentration-dependent decreases in relative survival are similar in all three cell lines, indicating that XRCC1 is not crucial for protecting cells from sodium chromate-induced cytotoxicity. Similarly the frequency of damaged metaphase cells was not affected by XRCC1 deficiency. However, the total number of Cr(VI)-induced chromosome aberrations was exacerbated by XRCC1 deficiency and the spectrum of chromosome damage changed dramatically. Specifically, chromatid and isochromatid lesions were the most prominent aberrations induced in the cell lines and XRCC1 was essential to reduce the formation of chromatid lesions. In addition, XRCC1 deficiency caused a dramatic increase in the number of chromatid exchanges indicating that it is involved in protection from Cr(VI)-induced chromosome instability.
Grlickova-Duzevik
Eliza
E
Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04104-9300, United States.
Wise
Sandra S
SS
Munroe
Ray C
RC
Thompson
W Douglas
WD
Wise
John Pierce
JP
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002840:Chromates / Q000494:pharmacology* / Q000633:toxicity; D002842:Chromatids / Q000187:drug effects / Q000235:genetics; D043171:Chromosomal Instability / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017670:Sodium Compounds / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors; D000076105:X-ray Repair Cross Complementing Protein 1
D002840:Chromates; D004268:DNA-Binding Proteins; D017670:Sodium Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C028982:sodium chromate(VI)