Biological monitoring screening of patients provided antineoplastic drugs including adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate, and vincristine.
The aim of the present study was to establish screening biomarkers of exposure to antineoplastic drugs administered to 11 patients undergoing cancer chemotherapy. Among the anticancer drugs administered were cyclophosphamide (all), Adriamycin (5 of 11), methotrexate (3 of 11), 5-fluorouracil (4 of 11), vincristine (3 of 11), megestrol acetate (1 of 11), and procarbazine (1 of 11). The noninvasive urinary parameters investigated were thioethers, D-glucaric acid, elements, and forward and reverse mutagenesis using bacterial bioassays. The data were analyzed in terms of the observed concentrations and those corrected for personal baseline. Personal baseline correction for parameters with significant nonexposure baseline levels was essential. While glucaric acid and thioethers were increased by the drug treatments, the correlations with baseline-uncorrected data showing an inverse relationship proved spurious, because saturation of the detoxification systems occurred at the high doses administered. Glucaric acid was also influenced by methotrexate and vincristine. Thioether content was affected by cyclophosphamide only. The forward mutagenesis assay was directly correlated to cyclophosphamide dose but the reverse assay was not, in the presence or absence of rat S9 fraction. The forward assay was not sensitive to the effects of smoking. Relative to controls, the elements changed by cyclophosphamide were K, S, and P. Those affected by Adriamycin were Ca, Mg, and Na; 5-fluorouracil affected Ca, Mg, Na, and C; methotrexate changed P and S. The forward mutagenesis assay and D-glucaric acid concentrations were the screening biomarkers best suited to monitoring for extent of exposure to these antineoplastic drugs.
Newman
M A
MA
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056.
Hee
S Q
SQ
Schoeny
R
R
Lowry
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D003404:Creatinine / Q000652:urine*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D004573:Electrolytes / Q000652:urine*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D005937:Glucaric Acid / Q000652:urine*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009152:Mutagenicity Tests; D013400:Sugar Acids / Q000652:urine*; D013440:Sulfides / Q000652:urine*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism
D004573:Electrolytes; D013400:Sugar Acids; D013440:Sulfides; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D003404:Creatinine; D005937:Glucaric Acid; D005472:Fluorouracil; D008727:Methotrexate