Genotoxicity of the herbicide 2,4-dichlorophenoxyacetic and a commercial formulation, 2,4-dichlorophenoxyacetic acid dimethylamine salt. I. Evaluation of DNA damage and cytogenetic endpoints in Chinese Hamster ovary (CHO) cells.

Genotoxicity of the 2,4-dichlorophenoxyacetic acid (2,4-D) and a commercially-used derivative, 2,4-D dimethylamine salt (2,4-D DMA), was evaluated in CHO cells using SCE and single cell gel electrophoresis (SCGE) assays. Log-phase cells were treated with 2.0-10.0 microg/ml of herbicides and harvested 24 and 36 h later for SCE analysis. Both agents induced significant dose-dependent increases in SCE, regardless of the harvesting time (2,4-D: r=0.98 and r=0.88, P<0.01, for 24 and 36 h harvesting times; 2,4-D DMA: r=0.97 and r=0.88, P<0.01, for 24 and 36 h harvesting times). Neither test compound altered cell-cycle progression or proliferative replication index (P>0.05), but the higher doses of both compounds reduced the mitotic index of cultures harvested at 24 and 36 h (P<0.05). A 90-min treatment with 2.0-10.0 microg/ml 2,4-D and 2,4-D DMA produced dose-dependent increases in the frequency of DNA-strand breaks detected in the SCGE assay, both in cultures harvested immediately after treatment and in cultures harvested 36 h later. The doses of 2,4-D and 2,4-D DMA were equally genotoxic in all of the assays. The results indicate that 2,4-D induces SCE and DNA damage in mammalian cells, and should be considered as potentially hazardous to humans.

[Participation of dexamethasone and E and C vitamins in the modulation of the hepatotoxic effect induced by fomesafen and 2,4-D amino herbicides, in rats ]. / Participacion de la dexametasona y las vitaminas E y C en la modulacion del efecto hepatotoxico inducido por los herbicidas fomesafen y 2,4-D amino, en ratas.

The fomesafen and 2,4-D amine herbicide induce cytotoxic effects at hepatic level in rats, such as: hepatomegaly, hyperplasia and increase in the enzymes activity which participate in the processes of peroxisomal beta-oxidation of fatty acids. In this work, the effect of vitamin E and C was evaluated, as well as, the dexamethasone in the modulation of these hepatotoxic effects. Sprague-Dawley rats were treated with the herbicides and with the agents to be evaluated. The different treatments were given during 15 days orally route. The herbicides combined with the dexamethasone and antioxidant agents were administrated only and simultaneously with the herbicides. Once concluded the different treatment, the rats were weighed and sacrificed. It was evaluated the liver size and liver fragments were obtained to determine the enzymatic activity of Fatty Acyl CoA-oxidase (FACO) and cellular number. The results showed that the hepatomegaly induced by fomesafen was inhibited by the vitamins and by the dexamethasone, while any effect was not observed in the group of rats treated with 2,4-D amine. None of the agents modulated the FACO activity induced by herbicides in treated rats. However, the dexamethasone showed a protective effect in the hyperplasia induced by two herbicides. The hepatotoxic effects induced by the herbicides responded to a different mechanism due to the differences of the effects observed at the antioxidant agents. On the other hand, the inhibition of the cellular proliferation by the dexamethasone does not keep relation with the responsible mechanisms of inducing the oxidant stress into FACO activity. Under experimental conditions of this study, the use of these agents does not guarantee protection against the hepatotoxic effects induced by the herbicides.