diethyl-maleate and hydroquinone

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Benzodioxoles; Butylated Hydroxyanisole; Caffeic Acids; Carcinogens; Carcinoma; Catechols; Cell Division; Hydroquinones; Kidney Neoplasms; Male; Maleates; Methylnitronitrosoguanidine; Organ Specificity; Papilloma; Phenols; Rats; Rats, Inbred F344; Stomach; Stomach Neoplasms

Hydroquinone, a metabolite of benzene, and acetaldehyde, a metabolite of ethanol, induce sister chromatid exchanges (SCEs) at relatively high concentrations. Because both compounds are reported to form glutathione conjugates, experiments were carried out to see if there was a synergistic effect when lower concentrations of both chemicals were added to human lymphocyte cultures. Hydroquinone (40 microM) increased SCEs in some individuals but not in others. However, the rate of SCE was more than doubled when cells were pretreated with diethyl maleate, which transiently depletes cellular glutathione. Acetaldehyde by itself increased SCEs at 100 microM, but it increased SCEs at 1 microM in the presence of diethyl maleate. When various concentrations of acetaldehyde were added to cultures containing 40 microM hydroquinone, synergism in the induction of SCEs was observed. The lowest effective concentration of acetaldehyde varied among individuals from 1 to 100 microM. These observations suggest that glutathione is involved in the detoxification of hydroquinone and acetaldehyde in lymphocytes and that the simultaneous presence of both chemicals may saturate this mechanism and thus increase their genotoxic potency. Genetic differences in glutathione metabolism may govern the concentration of acetaldehyde at which synergism occurs in different individuals.

Topics: Acetaldehyde; Cells, Cultured; Dose-Response Relationship, Drug; Drug Synergism; Humans; Hydroquinones; Lymphocytes; Maleates; Sister Chromatid Exchange