title: Chromium (VI) potentiates the DNA adducts (O(6)-methylguanine) formation of N-nitrosodimethylamine in rat: implication on carcinogenic risk.
abstract: Chromium (VI) [Cr(VI)] and nitrosamines such as N-nitrosodimethylamine (NDMA) exist commonly in the environment. To evaluate the potential influence of Cr(VI) co-exposure on the carcinogenic risk of NDMA, Female Wistar rats were treated with various concentrations of Cr(VI) and/or NDMA via drinking water for 15days and the DNA adducts (O(6)-methylguanine, O(6)-MeG) of NDMA in liver tissue was used as a bioindicator. The results showed that Cr(VI) synergistically enhanced the O(6)-MeG formation, which could lead to an increase in DNA damage and carcinogenic potential. Although Cr(VI) did not alter the CYP 2E1 enzyme activity, it decreased GSH content, which would be an potential mechanism for the potentiated O(6)-MeG formation by Cr(VI) co-exposure. These results would contribute to the development of quantitative risk assessment of NDMA or even for a group of nitrosamines under environmental mixture exposure.
authors.affiliation: Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Ma
authors.affiliation: Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
authors.forename: Zhaobin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. Electronic address: hujy@urban.pku.edu.cn.
authors.forename: Jianying
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002857:Chromium / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D060766:Drinking Water; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012306:Risk
chemical_list: D002274:Carcinogens, Environmental; D018736:DNA Adducts; D060766:Drinking Water; D002857:Chromium; C074702:chromium hexavalent ion; D006147:Guanine; C008449:O-(6)-methylguanine; D019392:Cytochrome P-450 CYP2E1; D004128:Dimethylnitrosamine
keywords: CYP 2E1 enzyme activity; Cr(VI); DNA adduct; GSH; Nitrosamines