Variability in cytogenetic adaptive response of cultured human lymphocytes to mitomycin C, bleomycin, quinacrine dihydrochloride, Co60 gamma-rays and hyperthermia.
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.
Krishnaja
A P
AP
Genetic Toxicology and Chromosome Studies Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. krishnja@apsara.barc.gov.in
Sharma
N K
NK
D000222:Adaptation, Physiological / Q000235:genetics*; D000328:Adult; D000970:Antineoplastic Agents / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity; D002877:Chromosomes, Human / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes / Q000737:chemistry; D004249:DNA Damage / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D005720:Gamma Rays; D005819:Genetic Markers; D006801:Humans; D006979:Hyperthermia, Induced; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D016685:Mitomycin / Q000633:toxicity; D011796:Quinacrine / Q000633:toxicity; D011836:Radiation Tolerance
D000970:Antineoplastic Agents; D003037:Cobalt Radioisotopes; D005819:Genetic Markers; D001761:Bleomycin; D016685:Mitomycin; D011796:Quinacrine