Teratogenic effects of cholinergic insecticides in chick embryos--IV. The role of tryptophan in protecting against limb deformities.
The mechanism by which organophosphate (OP) insecticides cause micromelia in embryonic chick limbs was examined using a tissue culture approach. Limb bud cells in micromass culture were assayed for their proliferative and chondrogenic activities, [3H]thymidine and 35SO4 = incorporation, respectively, into the trichloroacetic acid-insoluble constituents of the cell masses and/or the accumulation of 35S-labeled soluble macromolecular products in the culture medium. There was no obvious correlation between either the teratogenicity or toxicity of the insecticide in ovo and the inhibition of proliferation and chondrogenesis in vitro. In addition, nicotinamide, which prevents insecticide-induced micromelia in ovo, did not improve the proliferative and chondrogenic performance of insecticide-treated cells in culture. On the other hand, 2-pyridinealdoxime methochloride, which offers little or no protection against micromelia in ovo, did protect both the proliferative and chondrogenic activities of the limb bud cells in micromass culture. These observations suggest that the actions of the insecticides on the cells in culture are not the same as those that produce micromelia in ovo. L-Tryptophan antagonized OP insecticide-induced micromelia in the embryo. In micromass culture, a much greater concentration of tryptophan was needed to support the chondrogenic than the proliferative activities of the limb bud cells. Moreover, a greater concentration of tryptophan was needed to support the chondrogenic activities of the leg bud than the wing bud cells. These in vitro responses of the limb bud cells to tryptophan deprivation are analogous to the in ovo response of the limbs to the teratogenic OP insecticides. A possible explanation of the roles of tryptophan and nicotinamide in preventing the limb deformities is offered.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D003976:Diazinon / Q000633:toxicity; D005121:Extremities / Q000502:physiology; D007306:Insecticides / Q000633:toxicity*; D007700:Kinetics; D017880:Limb Deformities, Congenital; D009536:Niacinamide / Q000494:pharmacology; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000378:metabolism; D013329:Structure-Activity Relationship; D013723:Teratogens; D014364:Tryptophan / Q000494:pharmacology*
D007306:Insecticides; D011509:Proteoglycans; D013723:Teratogens; D009536:Niacinamide; D014364:Tryptophan; D003976:Diazinon