Craniofacial growth of immature rats following administration of vincristine and doxorubicin

The aim of the present study was to investigate the possible short-term eff ect of two anti-neoplastic drugs, vincristine and doxorubicin, on the crani ofacial skeleton in young rats. On the basis of findings from pilot experim ents, one dose of 0.0375 mg/kg vincristine or 1.0 mg/kg doxorubicin was giv en parenterally to inbred Long-Evans/Turku rats at 10 or 30 days of age, an d followed up until 30 or 50 days, respectively. Some 30-day-old rats recei ved two additional doses of the drugs, 3 and 6 days after the first injecti on. 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 exp eriment itself. The weights of the rats were recorded, a number of cranio f acial dimensions were measured, and the neurocranial volume determined in t he case of the most severely affected rats. The weight gain of the younger rats was retarded, as was that of the alder rats that received repeated drug injections. Most dimensions of the craniof acial skeleton were significantly smaller in the vincristine-treated young animals, and following multiple injections of vincristine or doxorubicin al so in the older ones when compared with the controls. Contrary to the gener al pattern, the measurements of the foramen magnum increased in the older r ats, 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 a dverse effect on the craniofacial growth and that the morphological changes are differential, rather than uniform.