Journal Article

Variability in cytogenetic adaptive response of cultured human lymphocytes to mitomycin C, bleomycin, quinacrine dihydrochloride, Co60 γ-rays and hyperthermia

A. P. Krishnaja and N. K. Sharma

in Mutagenesis

Published on behalf of United Kingdom Environmental Mutagen Society

Volume 23, issue 2, pages 77-86
Published in print March 2008 | ISSN: 0267-8357
Published online January 2008 | e-ISSN: 1464-3804 | DOI: https://dx.doi.org/10.1093/mutage/gem045
Variability in cytogenetic adaptive response of cultured human lymphocytes to mitomycin C, bleomycin, quinacrine dihydrochloride, Co60 γ-rays and hyperthermia

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Adaptive response (AR) is a well-documented phenomenon by which cells or organisms exposed to low dose of a genotoxicant become less sensitive to subsequent high-dose exposure to the same or another genotoxicant. AR, if induced can modify the efficacy leading to drug or radio-resistance, during anti-neoplastic drug or radiation treatment. Contradictions exist in AR induction by different genotoxicants with respect to the biomarkers, time schedules, and inter-individual variability, reflecting the complexity of AR in eukaryotic cells. In order to further ascertain these factors, AR induced by anti-neoplastic agents mitomycin C (MMC), bleomycin (BLM) and chemosterilant quinacrine dihydrochloride was examined in different donors and time schedules using cytogenetic biomarkers chromosome aberrations, sister chromatid exchanges and micronuclei (MN). BLM- and hyperthermia (HT)-induced cross-resistance to gamma rays and MMC/BLM, respectively, was also studied. Difference between MMC- and BLM-induced protective effects in biomarkers examined in the same donors was noticed. Adaptation to BLM and HT showed cross-resistance to chromosome damage induction by gamma rays and BLM/MMC, respectively. Cell cycle analysis indicated that adaptation is not caused by change in the rate of cell proliferation after challenge dose. MN as a chromosomal biomarker in large-scale population studies on AR is advocated, based on similar AR induced in all donors by MMC/BLM and rapid assessment in binucleated cells. Influence of certain genotypes on chromosomal biomarkers used in AR studies and role of AR in radiation and chemotherapy need to be further deciphered.

Journal Article.  4680 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics ; Genetics and Genomics

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