DNA synthesis and apoptosis in primary hepatocyte cultures from chick embryos after treatment with the herbicide 2,4-D

Chlorophenoxy herbicides belong to the peroxisome proliferator (PP) class of non-genotoxic hepatocarcinogens. The ability to stimulate DNA synthesis coupled with the ability to suppress or delay apoptosis may play a role in PP carcinogenesis. There are no conclusive data on the carcinogenicity of phenoxy herbicides. 2,4- dichlorophenoxyacetic acid (2,4-D) is an herbicide widely used in agriculture, forestry, and also in recreational areas. The widespread pattern of 2,4-D use may, therefore, pose a threat to avian organisms as well to other wild species. Primary hepatocyte cultures of chick embryos were used to assess the effects of 2,4-D on S-phase and apoptosis. Considering that PP tumorigenesis is species restricted, the PP Wy-14,643, a rodent hepatocarcinogen, was also tested. Both 2,4-D and Wy-14,643 at a dose level of 100 M induced a slight positive effect on DNA synthesis, as detected after BrdU incorporation, and reduced the number of apoptotic cells. These data support some experimental evidence that 2,4-D may act as a weak tumor promoter, although further experimentation is needed to confirm the results of the present study.