Chromium can reduce the mutagenic effects of benzo[a]pyrene diolepoxide in normal human fibroblasts via an oxidative stress mechanism.
The interaction of multiple carcinogens on human cells has not been extensively examined. This study reports the results of experiments in which normal human fibroblasts were exposed to both benzo[a]pyrene diolepoxide (BPDE) and potassium dichromate. The effect of four different treatment protocols on the cloning ability of the cells and the mutant frequency of the HPRT gene was determined. The combined treatment of both carcinogens caused a slightly greater than additive decrease in the cloning ability of the cells when compared to cells treated with the individual carcinogens. The result was the same regardless of the treatment protocol used in the experiment. The results of the mutant frequency experiments, however, varied dramatically with the protocol employed. The mutant frequency in cells which were simultaneously treated with both carcinogens was dramatically reduced from the mutant frequency found when cells were treated with BPDE alone. This antagonistic effect was not present when cells were either pretreated with potassium dichromate prior to BPDE or incubated with potassium dichromate following BPDE treatment. The observed antagonistic effect was the result of oxidative stress produced by chromium since it was completely or nearly completely reversed by the addition of either vitamin E or catalase to the cultures.
Tesfai
Y
Y
Departments of Chemistry and Biological Sciences, Western Michigan University, Kalamazoo, MI 49008, USA.
Davis
D
D
Reinhold
D
D
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002857:Chromium / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004347:Drug Interactions; D005347:Fibroblasts; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D016587:Antimutagenic Agents; D009153:Mutagens; D017382:Reactive Oxygen Species; D002857:Chromium; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D007041:Hypoxanthine Phosphoribosyltransferase