抗癌剤投与患者尿の変異原性に関する研究

Abstract

Mutagenic activity of urines from 43 patients with urogenital cancer was tested in the Salmonella typhimurium TA9S and TA100. All patients were hospitalized and were on usual hospital diets. They were ordered not to smoke during their hospital course and their renal and liver functions were almost normal. None of the patients received antibiotics during this experiment. 200 ml of each urine was concentrated 200-fold by adsorption with the XAD-2 resin. Ninety-four urine samples from 43 patients were divided into four groups: group I, 18 urine samples from 15 patients receiving no drugs; group 2, 27 urine samples from 24 patients receiving some drugs except for anti-cancer drugs; group 3, 39 urine samples from 16 patients receiving single anti-cancer drug; group 4, 10 urine samples from 5 patients receiving 2 anti-cancer drugs. A 24 hour urine was collected for groups 1 and 2, and a urine from the time of administration to the next early morning was collected for groups 3 and 4. The results are as follows: 1) None of urine concentrates of group 1 was mutagenic to either strain TA98 or TA100. 2) None of urine concentrates of group 2 was mutagenic to either strain TA98 or TA100. 3) Eight urine concentrates of group 3 were mutagenic. Though 5 urine concentrates from 3 patients receiving cyclophosphamide were not mutagenic to either strain TA98 or TA100, the urine concentrate obtained from 1 to 3 hours after administration of 1, 500 mg cyclophosphamide was mutagenic to the strain TA100. Four of 9 urine concentrates from 6 patients receiving adriamycin were mutagenic to the strain TA98 and/or TA100d two of 4 mutagenic urine concentrates were mutagenic to both strain TA98and TA100wo of 14 urine concentrates from 6 patients receiving cis-diamminedichloride platinum were mutagenic to the strain TA100. No mutagenic activity was detected in the urine of any of the patients receiving one of 4 anti-cancer drugs; actinomycin D, vinblastine, bleomycin or mitomycin C. 4) Four urine concentrates of group 4 were mutagenic. All of 2 urine concentrates from the patients receiving adriamycin and 5-f1uorouracil were mutagenic to the strain TA98. One of 3 urine concentrates from the patients receiving mitomycin C and cytosine arabinoside was mutagenic to the strain TA98. The urine concentrate from the patient receiving vincristine and actinomycin D was mutagenic to the strain TA98. No mutagenic activity was detected in the urine of the patients receiving vincristine and cytosine arabinoside, vincristine and pepleomycin, or methotrexate and pepleomycin. 5) Our results suggest that urinary metabolites of some anti-cancer drugs might act as an initiator on the urothelium. Although at the present time the detection of mutagenic activity in the urine does not necessarily predict carcinogenesis of the urothelium, the physician who uses anti-cancer drugs should be aware of delayed sequelae on the urinary tract.