Osteolathyrogenic effects of malathion in Xenopus embryos

Malathion, an organophosphorus insecticide, has been found previously to cause developmental defects such as enlargement of the atria and aorta and bent notochord in Xenopus laevis. Since these defects are similar to those caused by known lathyrogens, the effects of malathion on collagen biochemistry and structure were studied. Embyros were exposed to malathion or its metabolite malaoxon during the first 4 days of development. Notochords of malathion- and malaoxon-treated embryos were bent ventrally between the third and sixth somites and were enlarged. Ultrastructural examination of the postanal tail notochord showed that the elastic externa was disorganized and less dense and the sheath had fewer, more disorganized fibers. Embryos exposed in culture displayed a concentration-dependent reduction in ascorbate and hydroxyproline. Malathion and malaoxon inhibited the activities of lysyl oxidase (I50s of 0.7 and 8.7 nM, respectively) and proline hydroxylase (I50s of 58 microM and 49.9 nM, respectively) in homogenates of Xenopus embryos. These data suggest that malathion and malaoxon alter posttranslational modification of collagen, with resultant morphological defects in connective tissue.