Abstract
Measurement of plasma 11-hydroxycorticosteroid levels after vinblastine sulfate (VLB) injection (1 mg/kg) into nonadrenalectomized rats showed that corticosteroid levels were elevated by a factor of two over control level within 3 hr after injection, increasing to a factor of four within 12 hr. Since adrenal steroids were known to cause thymic involution associated with an inhibition of nucleic acid synthesis, VLB effects on thymus were compared in adrenalectomized and nonadrenalectomized rats. VLB (0.33–1.0 mg/kg) caused thymic weight loss in adrenalectomized rats. Incorporation of [ 14C]thymidine and [ 3H]uridine into cold-acid-insoluble material by thymocytes, obtained from adrenalectomized rats after they had been injected with similar doses of VLB, was also inhibited. The magnitude of each of these effects was similar to that seen in nonadrenalectomized rats. It was concluded that adrenal steroid release did not play a major role in the thymolytic effects of VLB. Adrenalectomized rats were shown to be more sensitive to the lethal effects of VLB than were nonadrenalectomized rats. Small doses of cortisol administered simultaneously with VLB could protect rats from the lethal effects of this agent.
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