S. Karsila et al., Effect of methotrexate alone and in combination with vincristine on craniofacial morphology in growing rats, ACT ODON SC, 57(5), 1999, pp. 271-276
Craniofacial growth in young Long-Evans/Turku strain rats was studied follo
wing administration at different intervals of the antineoplastic agent meth
otrexate (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/k
g MTX, while single and repeated doses of 1.0 mg/kg MTX, or of the combinat
ion of MTX (1.0 mg/kg) and VCR (0.05 mg/kg), could be used for the 30-day-o
ld 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 a
nd males were pooled. Administration of MTX alone or combined with VCR caus
ed disturbed craniofacial growth, which was already evident following 1 sin
gle injection of MTX in the younger rats (10 to 30 days) and after repeated
injections (every third dal;) of MTX alone or combined with VCR in the old
er rats (30 to 50 days). The body weights of all the medicated rats were in
itially 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 receive
d a single injection of MTX, but not after repeated injections. We conclude
that the antineoplastic agent MTX alone or in combination with VCR adminis
tered at short intervals with pharmacologically adjusted doses has a short-
term effect on the craniofacial skeleton of growing rats.