Interactions of nitrilotriacetic acid (NTA) with Cr(VI) compounds in the induction of gene mutations in cultured mammalian cells.
We used the V79 Chinese hamster cell line to detect the induction by NTA of 6-thioguanine resistance, due to mutation at the HGPRT locus, with direct and indirect mutagens as positive controls. NTA was tested within the 10(-4)-1.5 X 10(-2) M concentration range: although it was cytotoxic above the 10(-2) M dose, it did not increase the frequency of mutations at any of the tested concentrations, independently of metabolic activation (rat-liver S9 fraction). NTA is known to dissolve heavy metals and therefore to increase their genotoxicity. We found that an insoluble Cr(VI) compound, lead chromate (PbCrO4), was not cytotoxic nor mutagenic on V79 cells, probably because it is taken up by the cells very slowly, whereas the presence of NTA (2.5 X 10(-3) M in water) elicited a direct cytotoxicity and mutagenicity, which was dose-dependent from 5 X 10(-5) M to 10(-4) M PbCrO4. This effect was due to solubilization of the chromate anion by NTA, as determined by comparing spectrophotometric determinations of Cr(VI) in PbCrO4 treatment solutions with a mutagenicity titration curve obtained with a completely soluble Cr(VI) salt (potassium dichromate, K2Cr2O7).
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002840:Chromates / Q000494:pharmacology / Q000633:toxicity*; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D007854:Lead / Q000633:toxicity*; D009154:Mutation; D009571:Nitrilotriacetic Acid / Q000633:toxicity*; D017680:Potassium Compounds; D012995:Solubility; D013866:Thioguanine / Q000494:pharmacology
D000085:Acetates; D002840:Chromates; D017680:Potassium Compounds; D007854:Lead; C027373:potassium chromate(VI); C031895:lead chromate; D013866:Thioguanine; D009571:Nitrilotriacetic Acid