Effect of methotrexate alone and in combination with vincristine on craniofacial morphology in growing rats

Craniofacial growth in young Long-Evans/Turku strain rats was studied following administration at different intervals of the antineoplastic agent methotrexate (MTX) and of a combination of two agents, MTX and vincristine (VCR). The 10-day-old rats tolerated only 1 subcutaneous injection of 0.75 mg/kg MTX, while single and repeated doses of 1.0 mg/kg MTX, or of the combination of MTX (1.0 mg/kg) and VCR (0.05 mg/kg), could be used for the 30-day-old rats. The rats were killed 20 days after the start of the experiment, i.e. at 30 or 50 days of age, respectively; their weights were recorded and a total of 12 craniofacial dimensions were measured. Owing to the relatively few significant sex differences, the dimensions recorded for the females and males were pooled. Administration of MTX alone or combined with VCR caused disturbed craniofacial growth, which was already evident following 1 single injection of MTX in the younger rats (10 to 30 days) and after repeated injections (every third day) of MTX alone or combined with VCR in the older rats (30 to 50 days). The body weights of all the medicated rats were initially retarded and catch-up growth, i.e. a return to control body weight levels, occurred by the end of the experiment only in the rats that received a single injection of MTX, but not after repeated injections. We conclude that the antineoplastic agent MTX alone or in combination with VCR administered at short intervals with pharmacologically adjusted doses has a short-term effect on the craniofacial skeleton of growing rats.