Limbs from rat fetuses exposed to the alkylating agent chlorambucil on day 14 of gestation undergo abnormal skeletogenesis (Brummett & Johnson, 1979). The abnormal developmental sequences are manifest as marked disruption of chondrogenesis and ossification. The present study examines some of the biochemical factors normally related to initial mineralization and their possible alteration during teratogenesis.

The specific activities of the acid, alkaline and pyro-phosphatases were determined for normal and abnormal (drug-treated) fetal rat limbs during days 15–17 of gestation, the period of cartilage-model calcification. This was done to determine if altered enzymatic activity leading either to depressed localized phosphate levels or hydroxyapatite crystal growth inhibition would account for the decreased calcification. The level of alkaline phosphatase increased dramatically (sixfold in 3 days), in association with normal cartilage formation. In the abnormal limbs, this rise was only half as great. Pyrophosphatase and acid phosphatase activity in both normal and abnormal limbs did not change over the 3-day period.

The normal concentrations of ions critical to calcification, i.e. phosphate, calcium and magnesium, were determined for maternal serum, amniotic fluid, whole fetuses and fetal limbs. Mean phosphate and calcium levels increased slightly in the limbs with increasing gestational age. The ion levels in drug-treated fetuses were within normal limits except in amniotic fluid where phosphate was increased significantly on day 17. Also the protein concentration in the fluid was elevated on day 16 and 17.

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