The oncogenic effect of immunosuppressive (cytotoxic) agents in (NZB X NZW) mice. I. Long-term treatment with azathioprine and ifosfamide.

The increased incidence of neoplasia in the chronic use of immunosuppressive agents has been linked to a variety of factors including age, dose, agent, and frequency of administration. In this study azathioprine (az) and ifosfamide (ifo) were given both daily and weekly to female (NZB X NZW) mice over a period of 14 or 16 months in various dose regimens. Daily treatment with both agents prolonged survival time significantly but induced an apparently dose-related increase in tumor frequency. Intermittent ifo therapy produced neoplasia and survival results comparable to daily treatment, whereas intermittent az failed to extend longevity or produce malignancies. Varying the age of the mice (180 vs. 120 days) at the outset of treatment did not materially affect results in any respect. Ifo is less toxic than az in doses prolonging survival.