Inhibition of metabolic cooperation between Chinese hamster V79 cells by structurally diverse teratogens.

Abstract

Cell-cell communication through chemical messengers is a fundamental event required for the differentiation of embryonal cells. Interference with this process by xenobiotics may disrupt embryogenesis. Chinese hamster cells (V79) which display a specific form of cell-cell communication called metabolic cooperation were cultured in the presence of structurally diverse chemical teratogens. Among them were 12-O-tetradecanoyl-phorbol-13-acetate (TPA), diphenylhydantoin (DPH), warfarin, and a series of monoalkyl ethers of ethylene glycol with alcohol chain lengths from methyl to butyl. Sodium saccharin and ascorbic acid were examined to represent two chemicals which have been thoroughly tested for teratogenic effects in laboratory animals and cause no birth defects. Recovery of 100 6-thioguanine-resistant V79 (6-TGr) cells in coculture with 400,000 6-thio-guanine-sensitive V79 (6-TGs) cells in the presence of 6-thioguanine (6-TG) and the chemical agent was measured. In amounts that neither interfered with colony forming ability nor caused cytostasis when 100 6-TGr cells were plated alone, all of the substances except for saccharin and vitamin C increased the number of surviving 6-TGr cells in a concentration-related manner. The recovery was increased by the presence of TPA (to 100% by 4 ng/ml), DPH (from 26% at 91 microM to 43% at 274 microM), warfarin (from 15.5% at 162 microM to 44.5% at 487 microM) and to variable extents by all five glycol ethers. The most efficacious in the latter group of compounds was the isopropyl ether which raised 6-TGr recovery from 8% at 0.017 M to 66% at 0.087 M. Based on the evidence accumulated by previous studies involving TPA, we postulate that the teratogens employed inhibited metabolic cooperation. These observations suggest that V79 cells may be suitable to study inhibition of cell-cell communication as a mechanism of teratogenesis.