title: Do organophosphate insecticides inhibit the conversion of tryptophan to NAD+ in ovo?
abstract: The hypothesis that organophosphate (OP) insecticides reduce the NAD+ levels of chick embryos by inhibiting kynurenine formamidase was tested. Fertile chicken eggs at 3 days of incubation were treated with a teratogenic dose of the organophosphate insecticide diazinon (DZN) in the presence or absence of exogenous L-tryptophan or nicotinamide, or one of the metabolic intermediates (L-kynurenine, 3-hydroxyanthranilic acid, quinolinic acid) between tryptophan and NAD+. By day 10 of development, DZN reduced the NAD+ content of the hind limbs of the embryos to less than 20% of normal and by day 15 it caused severe type I and type II teratogenic responses. The co-presence of tryptophan or one of its metabolites served to maintain the NAD+ levels of DZN-treated embryos close to or above normal and significantly alleviated the symptoms of type I teratisms. Tryptophan is virtually as effective as most of its metabolites in suppressing the effects of DZN on the NAD+ content and physical development of the embryos. This equivalence does not support the proposition that the inhibition of kynurenine formamidase causes the lowered NAD+ levels involved in OP-induced type I teratogenesis. It is consistent with the concept that the insecticide acts to decrease the availability of tryptophan to the embryo.
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D005558:Arylformamidase / Q000037:antagonists & inhibitors; D002642:Chick Embryo / Q000187:drug effects; D003976:Diazinon / Q000009:adverse effects; D005260:Female; D007306:Insecticides / Q000009:adverse effects*; D009024:Morphogenesis / Q000187:drug effects; D009243:NAD / Q000378:metabolism*; D010063:Ovum / Q000187:drug effects / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D007306:Insecticides; D009243:NAD; D014364:Tryptophan; D005558:Arylformamidase; D003976:Diazinon