To minimize the nausea and vomiting experienced by a high percentage of patients beginning procarbazine therapy, single or divided doses of 2 to 4 mg/kg/day for the first week are recommended. Daily dosage should then be maintained at 4 to 6 mg/kg/day until maximum response is obtained or until the white blood count falls below 4000 or the platelets fall below 100,000. When maximum response is obtained, the dose may be maintained at 1 to 2 mg/kg/day. Upon evidence of hematologic or other toxicity, the drug should be discontinued until there has been satisfactory recovery. After toxic side effects have subsided, therapy may then be resumed at the discretion of the physician, based on clinical evaluation and appropriate laboratory studies, at a dosage of 1 to 2 mg/kg/day.

LI210 cells growing in log phase were collected by centrifugation and were resuspended in complete media containing 1% horse serum and 100 U/ml penicillin and 100 ng/ml streptomycin at 3 x IO6cells/ml. After a 10-min preincubation period at 37°C,either procarbazine or one of its various metabolites were added in ethanol (<50 ^1/ml media); control cells received an equal volume of ethanol alone. The treatment was carried out in a COz incubator and tubes were gently shaken every 10 min. After incubation, 5 ml of ice-cold Dulbecco's phosphatebuffered salt solution (pH 7.4) was added to each tube and the cells pelleted as above. The wash step was repeated and cells resuspended in Dulbecco's phosphate-buffered salt solution at a cell concentration of 1 x 106/ml. When alkaline-elution analysis was performed, cells were held on ice for up to 1 h to inhibit cellular repair processes prior to analysis. When growth experiments were performed, cells were resus pended in regular culture media containing antibiotics and allowed to reestablish growth.