US EPA

1357807 

Journal Article 

Sodium Arsenite Potentiates the Clastogenicity and Mutagenicity of DNA Crosslinking Agents 

Lee T-C; Lee, KC; Tzeng, YJ; Huang, RY; Jan, KY 

1986 

Yes 

Environmental Mutagenesis
ISSN: 0192-2521
EISSN: 1930-238X 

NIOSH/00165106 

8 

1 

119-128 

eng 

Effect of sodium-arsenite (7784465) (AS) on the clastogenicity and mutagenicity of cis-diaminedichloroplatinum (15663271) (cisPt) and 8-methoxypsoralen (298817) (MOP) in the presence of long wave ultraviolet (UV) light was studied. Chinese-hamster ovary (CHO) cells and human skin fibroblasts (HSF) were exposed to various concentrations of cisPt. To observe the response to MOP and UV light; cells were treated with various concentrations of MOP, exposed to 60 Joules/square meter (J/m2), washed out, and reirradiated with UV light at 160J/m2. Post treatment with AS synergistically increased percentages of aberrant metaphases induced by cisPt in CHO cells and HSF. Chromatid breaks and exchanges increased in jointly treated CHO cells and HSF. A large increase of shattered metaphases was observed when higher doses of cisPt were used in joint treatment. Effect of AS post treatment on chromosomal aberrations induced by cisPt was time dependent. Post treatment with 5 and 10 micromolar of AS synergistically increased cytotoxicity and mutation frequency at the hypoxanthine-guanine-phosphoribosyl-transferase (HGPRT) locus induced by cisPt in CHO cells. A linear relationship existed between mutation frequency and relative percent survival of cisPt exposure, with or without AS post treatment. This indicated that AS did not condition the HGPRT locus to become hypermutable in cells treated with cisPt. An appreciable amount of chromosomal aberrations was found in the presence of MOP after UV light irradiation. One micromolar AS induced a limited amount of chromosome aberrations in HSF, but coclastogenicity was clearly demonstrated. This suggested that coclastogenicity and comutagenicity of AS may be more hazardous than direct genotoxicity of AS by itself. The authors state that the coclastogenicity of arsenic may accelerate the process of carcinogenesis. 

DCN-151693; In vitro studies; Humans; Rodents; Arsenic compounds; Platinum compounds; Ultraviolet radiation; Deoxyribonucleic acids; Mutagenicity; Carcinogenicity