Induction of sister chromatid exchanges by the peroxisome proliferators 2, 4-D, MCPA, and clofibrate in vivo and in vitro
- 1 June 1984
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 5 (6), 703-707
- https://doi.org/10.1093/carcin/5.6.703
Abstract
Phenoxy acid herbicides 2,4-dichlorophenoxyacetic acid (2, 4-D) and 4-chloro-2-methylphenoxyacetic add (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-α- 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 intra-gastric 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 adds 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 adds. The present results support the data which indicate that 2,4-D, MCPA, and clofibrate do not act as direct DNA-damaging agents.This publication has 29 references indexed in Scilit:
- MITOGENIC AND CARCINOGENIC EFFECTS OF A HYPOLIPIDEMIC PEROXISOME PROLIFERATOR, [4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO]ACETIC ACID (WY-14,643), IN RAT AND MOUSE-LIVER1979
- Enhancement of Fatty Acyl-CoA Oxidizing Activity in Rat Liver Peroxisomes by Di-(2-Ethylhexyl)PhthalateThe Journal of Biochemistry, 1978
- Rat liver peroxisomes catalyze the beta oxidation of fatty acids.Journal of Biological Chemistry, 1978
- The genetic toxicology of phenoxy acids other than 2,4,5-TMutation Research/Reviews in Genetic Toxicology, 1978
- Malignant Tumors in Rats Fed Nafenopin, a Hepatic Peroxisome Proliferator 2JNCI Journal of the National Cancer Institute, 1977
- Induction of sister chromatid exchanges in Chinese hamster cells by carcinogenic mutagens requiring metabolic activationMutation Research, 1977
- A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug.Proceedings of the National Academy of Sciences, 1976
- HEPATOCELLULAR CARCINOMAS IN ACATALASEMIC MICE TREATED WITH NAFENOPIN, A HYPOLIPIDEMIC PEROXISOME PROLIFERATOR1976
- In vivo BrdU-33258 Hoechst analysis of DNA replication kinetics and sister chromatid exchange formation in mouse somatic and meiotic cellsChromosoma, 1976
- Approximate Significance Levels of the Behrens-Fisher TestBiometrics, 1964