Species variation in susceptibility to methylnitrosourea-induced immunosuppression.

Methylnitrosourea (MNU) was shown to suppress the cell-mediated immune system of mice. Cutaneous allografts were retained longer than controls in mice treated with 25 or 50 mg/kg MNU. The lymphocyte blast transformation (LBT) responses to the mitogens concanavalin A (con A) and lipopolysaccharide (LPS) of splenocytes from treated mice were also suppressed three days following treatment. By 7 and 42 days, however, the LBT responses to con A were higher than the controls for the 10 and 25 mg/kg dose groups. The rebound in the response to LPS was not nearly so pronounced and at 7 and 42 days was still suppressed for the 50 mg/kg dose group. In additional experiments, the LBT response of normal murine splenocytes to con A and LPS were significantly suppressed after exposure to 25 micrograms/ml MNU, and the LBT response of human lymphocytes to con A was suppressed after exposure to 60 micrograms/ml MNU. The results of these studies were compared to previous experiments in cats. It was concluded that cats are more immunosuppressed by MNU than mice, and suppression of the LBT response following exposure of normal lymphocytes to MNU is in the order cats greater than mice greater than humans.