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EFFECT OF CHEMOTHERAPY ON THE IN VIVO FREQUENCY OF GLYCOPHORIN A "NULL" VARIANT ERYTHROCYTES
Citation:
Bigbee, W., A. Wyrobek, R. Langlois, R. Jensen, AND R. Everson. EFFECT OF CHEMOTHERAPY ON THE IN VIVO FREQUENCY OF GLYCOPHORIN A "NULL" VARIANT ERYTHROCYTES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-90/286.
Description:
A human in vivo somatic cell assay based on the enumeration of variant erythrocytes lacking expression of an allelic form of the Cell-surface sialoglycoprotein, glycophorin A, was applied to the study of blood samples from patients obtained prior to, during, and following chemotherapy for malignant disease in order to determine the effect of mutagenic chemical agents on the frequency of variant cells. n 22 patients assayed prior to therapy, the mean variant cell frequency was 11.9 per million, which was not significantly different from that observed in healthy controls. n an initial cross-sectional survey, blood samples were obtained at various times during and after therapy from 30 patients diagnosed with a variety of malignancies who were treated with one or more known mutagenic agents including adriamycin, bleomycin, cis-platinum, cyclophosphamide, dacarbazine, etoposide, lomustine, mechlorethamine, melphalan, mitomycin C, and procarbazine. ignificant elevations in the mean frequency of variant cells over pre-therapy and normal levels were observed in samples obtained during and after therapy. n a time-series study, 14 breast cancer patients treated with CAF (cyclophosphamide, adriamycin, 5-fluorouracil), CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or VMF (vinblastine, methotrexate, 5-fluorouracil) adjuvant chemotherapy were sampled repeatedly during and after therapy. or the CAF and CMF patients an increase in the frequency of variant cells was observed with a lag in the appearance of induced continued variants after initiation of therapy; variant frequencies gradually increased during therapy reaching a maximum at or shortly after the end of therapy, then declined to near pre-therapy levels within 6 months. he maximum level of induced variants ranged from 2- to 7-fold over pre-therapy or normal levels depending on the combination of agents used. he breast cancer patients treated with both adriamycin and cyclophosphamide showed consIstent elevations in the frequency of variant cells; patients treated only with cyclophosphamide showed lower and more variable elevations. he data demonstrate that mutagenic chemotherapy agents induce elevated levels of glycophorin A variant erythrocytes consistent with hypothesis that variant cells result from somatic mutation. he elevations in variant cells were transient, suggesting that these agents primarily affect the rapidly cycling committed erythroid cell population.