Craniofacial growth of immature rats following administration of vincristine and doxorubicin.

Abstract

The aim of the present study was to investigate the possible short-term effect of two anti-neoplastic drugs, vincristine and doxorubicin, on the craniofacial skeleton in young rats. On the basis of findings from pilot experiments, one dose of 0.0375 mg/kg vincristine or 1.0 mg/kg doxorubicin was given parenterally to inbred Long-Evans/Turku rats at 10 or 30 days of age, and followed up until 30 or 50 days, respectively. Some 30-day-old rats received two additional doses of the drugs, 3 and 6 days after the first injection. Controls were given physiological saline. A total of 310 rats were used: 40 for the pilot study, 180 medicated, and 90 control animals for the experiment itself. The weights of the rats were recorded, a number of craniofacial dimensions were measured, and the neurocranial volume determined in the case of the most severely affected rats. The weight gain of the younger rats was retarded, as was that of the older rats that received repeated drug injections. Most dimensions of the craniofacial skeleton were significantly smaller in the vincristine-treated young animals, and following multiple injections of vincristine or doxorubicin also in the older ones when compared with the controls. Contrary to the general pattern, the measurements of the foramen magnum increased in the older rats, a feature associated with the decrease in brain cavity volume observed in those that received vincristine. These findings indicate that anti-neoplastic agents can have a short-term adverse effect on the craniofacial growth and that the morphological changes are differential, rather than uniform.