PROTECTION OF MICE FROM TERATOGEN-INDUCED CLEFT-PALATE BY EXOGENOUS METHIONINE

A major challenge for biomedical research is the reduction and/or prev ention of congenital craniofacial abnormalities which can be induced b y some extrinsic toxicants such as retinoic acids (e.g. isotretinoin, Accutane (R)) and glucocorticoids (corticosteroid hormones) during emb ryonic craniofacial morphogenesis. Our present studies using a genetic ally susceptible mouse strain (B10.A) indicate that the teratogenic ac tions of exogenous retinoic acid or glucocorticoid in secondary cleft palate induction can be largely reduced or even completely rescued by subsequent administration of methionine. The greatest reduction in fre quency of all-trans retinoic acid- or triamcinolone-induced secondary cleft palate was obtained by a single-dose IP administration of methio nine at 187 mg/kg to pregnant mice an E13 21 hr. It appears that detri mental toxic effects were not observed in mice treated with this thera peutic level of methionine. Our present findings support the need for further research into the role of exogenous methionine in cleft palate reduction, that will provide a biological rationale for considering m ethionine as a therapeutic agent.