Induction of sister chromatid exchanges by the peroxisome proliferators 2,4-D, MCPA, and clofibrate in vivo and in vitro.
Phenoxy acid herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) have been found to induce proliferation of peroxisomes in the liver cells of rodents in the same manner as the hypolipidemic drug clofibrate. Both phenoxy acid herbicides and clofibrate (ethyl-alpha-p- chlorophenoxyisobutyrate ) are suspected carcinogens. The present study reports the effect of these agents on the induction of sister chromatid exchange (SCE) in the blood lymphocytes of exposed rats (100 mg/kg with 2,4-D and MCPA, 200 mg/kg with clofibrate for 2 weeks in one intragastric dose/day), in the bone marrow cells of exposed Chinese hamsters (100 mg/kg, treatments as above), and in Chinese hamster ovary (CHO) cells in vitro (10(-5), 10(-4), and 10(-3) M, for 1 h). In the experiments in vitro, the effects of purified 2,4-D and MCPA phenoxy acids were studied, in addition to those of the commercial herbicide formulations and clofibrate. No increase of SCE frequency was observed in the blood lymphocytes of the exposed rats in comparison with the controls. In the bone marrow cells of the exposed Chinese hamsters, a slight increase of SCE was found in the group treated with MCPA but not in the groups treated with 2,4-D or clofibrate. A slight increase in the number of SCEs was characteristic of all the treated CHO cell cultures, both with and without a rat liver microsomal activation system (S9 mix). No clear dose-related effects, however, could be discerned with any of the compounds, and no differences in the SCE induction were observed between the commercial herbicide products and the purified phenoxy acetic acids. The present results support the data which indicate that 2,4-D, MCPA, and clofibrate do not act as direct DNA-damaging agents.
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D002994:Clofibrate / Q000633:toxicity*; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D006016:Glycolates / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D006016:Glycolates; D015084:2,4-Dichlorophenoxyacetic Acid; D008456:2-Methyl-4-chlorophenoxyacetic Acid; D002994:Clofibrate