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PubMed1976

[Prevention of abnormalities induced by 2 organophosphate insecticides (parathion and bidrin) in quail embryos].

When Quail embryos, injected with bidrin at the unincubated stage, are treated with nicotinamide, beak and leg abnormalities are prevented, but niacin has no beneficial effect on the axial deformities caused by both parathion and bidrin. In contrast, vertebral defects are greatly reduced by giving pralidoxim, an antidote known and used in organophosphorus intoxications. But this compound has no effect on beak and leg damage caused by bidrin. Two other cholinesterase reactivators, diacetylmonoxime and monoisonitrosoacetone have any effect on organophosphorus abnormalities and have no antiteratogenic action either on the beak and legs or on the vertebral column. From these observations the multiple causes of teratogenic effects induced by organophosphorus compounds are evident. Both aspects of teratogenesis, one related to the nicotinamide level, and the other related to the physiology of the cholinergic system are discussed.

Abnormalities, Drug-Induced↗
PubMed1986

DNA adducts of halogenated hydrocarbons.

Although formation of DNA adducts has been postulated for several halomethanes, no chemical identification of such adducts has been performed so far. There is, however, evidence that methyl chloride does not act biologically as a DNA methylating agent. 1,2-Dichloroethane and 1,2-dibromoethane are activated through conjugation with glutathione. There is some evidence for formation on an N-7 adduct of guanine which carries an ethyl-S-cysteinyl moiety. Extensive work has been published on adducts of vinyl chloride, both in vitro and in vivo. The major DNA adduct is 7-(2-oxoethyl)guanine; a minor adduct appears to be N2,3-ethenoguanine. Other "etheno" adducts, i.e., 1,N6-ethenoadenine and 3,N4-ethenocytosine, are readily formed with DNA, vinyl chloride, and a metabolizing system in vitro and with RNA in vivo, but are usually not detected as DNA adducts in vivo. The data on DNA alkylation by vinyl chloride (and vinyl bromide) metabolites are compared with those of structurally related compounds (acrylonitrile, vinyl acetate, vinyl carbamate).

Alkylating Agents↗