EFFECT OF PURIFICATION, THEOPHYLLINE AND SODIUM-FLUORIDE ON HISTAMINE-RELEASE PRODUCED BY ANTINEOPLASTIC DRUGS ON RAT MAST-CELLS - A DISTINCTIVE MECHANISM OF ACTION FOR CARBOPLATIN

The antineoplastic drugs, cytarabine, ifosfamide, vinorelbine, doxorubicin, asparaginase and carboplatin, elicit histamine release from rat pleural and peritoneal mast cells. Both cell populations do not show heterogeneity in their response to stimulation by any of these drugs, with the exception of cytarabine, which activates pleural mast cells at lower concentrations. When these cells arc purified with Percoll, L-asparaginase, vinoreibine and cytarabine completely lose their capability of inducing histamine release in both cell populations, while the other drugs still show the same pattern of response as with unpurified cells. These results indicate that some membrane component crucial for the action of vinorelbine, L-asparaginase and cytarabine is lost during the purification procedure. Pretreatment of the cells with theophylline completely inhibits the response to cytarabine, ifosfamide, vinorelbine and asparaginase, and inhibits the response to doxorubicin by up to 75% only. Theophylline does not change the response to carboplatin. Sodium fluoride does not change the response to any of the drugs tested. with the exception of carboplatin, in which case a complete inhibition is observed. In conclusion, carboplatin activates rat mast cells through a completely different mechanism of action with respect to the other drugs studied.