Multiple biological markers in germ cell tumor patients treated with platinum-based chemotherapy Journal Article
| Authors: | Perera, F. P.; Motzer, R. J.; Tang, D.; Reed, E.; Parker, R.; Warburton, D.; O'Neill, P.; Albertini, R.; Bigbee, W. L.; Jensen, R. H.; Santella, R.; Tsai, W. Y.; Simon-Cereijido, G.; Randall, C.; Bosl, G. |
| Article Title: | Multiple biological markers in germ cell tumor patients treated with platinum-based chemotherapy |
| Abstract: | The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Blood samples from 36 germ cell tumor patients receiving chemotherapy with either cisplatin or carboplatin in combination with other drugs [etoposide or vinblastine, cyclophosphamide, dactinomycin, and bleomycin (VAB-6) were analyzed for the presence of 7 different biological markers. The biomarkers included platinum-protein adducts, platinum-DNA adducts, sister chromatid exchange (SCE), micronuclei (MN), and somatic gene mutation at the hypoxanthine phosphoribosyl transferase (HPRT) locus and the glycophorin A (GPA) loci (NO and NN). Patients were asked to donate 9 serial blood samples: a pretreatment sample followed by another drawn 12-24 h after each of four cycles of treatment and a final sample provided 3-6 months after the last cycle. Most individuals gave 7-8 samples; 7 individuals donated aU 9. Because of limited amounts of cells in some cases, it was not possible to carry out all 7 assays on every sample. Pt-protein adducts, Pt-DNA adducts, and SCE showed a direct and consistent effect of treatment and were very highly correlated. A significant correlation was also seen between both Pt-protein and Pt-DNA adducts and HPRT mutation. All of the post-treatment samples were significantly elevated compared to the baseline sample. These markers also remained elevated 3-6 months after the end of treatment. By contrast, MN, HPRT mutation, and GPA mutation (both NO and NN variants) showed varying patterns of dose response, probably reflective of the differing biology of these markers scored in lymphocytes (MN and HPRT) and erythrocytes (GPA). MN were significantly elevated in the nosttreatment samples drawn at cycles 2 and 3. Although induction of HPRT mutation was only of marginal significance, results here are for the mutant frequency determination assay only. In progress is the potentially more informative analysis of the type of mutations by Southern blot and the sequencing of mutations to look for characteristic mutational spectra. The GPA assay showed a significant increase over baseline in samples drawn after cycles 3 and 4 (NO variants) and after cycles 2, 3, and 4 (NN variants). The level of GPA mutation (both NO and NN variants) was clearly elevated even 3-6 months after the last cycle of chemotherapy. Correlations were seen between HPRT and MN as well as between GPA NO and GPA NN variants. Analysis of biomarkers by treatment group does not reveal a consistent pattern or trend across all cycles. However, platinum combined with VAB-6 appears to have a greater effect than platinum plus etoposide on SCE, MN, and HPRT at several time points. This may be explained by a greater combined genotoxicity of VAB-6 compared to etoposide and platinum. There was also marked variation in response between individuals receiving the same chemotherapy dose and sampled at the same time point. © 1992, American Association for Cancer Research. All rights reserved. |
| Keywords: | adolescent; adult; clinical article; gene mutation; mutation; cisplatin; cancer combination chemotherapy; biological marker; biological markers; carboplatin; etoposide; gene locus; cyclophosphamide; drug effect; vinblastine; dna; dactinomycin; bleomycin; sister chromatid exchange; dna adduct; neoplasms, germ cell and embryonal; germ cell tumor; middle age; hypoxanthine phosphoribosyltransferase; micronucleus; glycophorin; human; male; female; priority journal; article; glycophorin a; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; micronucleus tests; atomic absorption spectrometry |
| Journal Title: | Cancer Research |
| Volume: | 52 |
| Issue: | 13 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1992-07-01 |
| Start Page: | 3558 |
| End Page: | 3565 |
| Language: | English |
| PUBMED: | 1319825 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 30 July 2019 -- Source: Scopus |
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