Interindividual variation in the responses of cultured human lymphocytes to exposure from DNA damaging chemical agents: Interindividual variation to carcinogen exposure |
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| Affiliation: | 1. Wallenberg Laboratory, Nucleic Acid Biochemistry, University of Lubd, Fack 7031, S-220 07 Lund 7, Sweden;2. Department of Clinical Genetics, University Hospital, S-221 85 Lund, Sweden;3. Unit of Community Care Sciences, S-240 10 Dalby, Sweden;1. Serbian Institute of Occupational Health “Dr Dragomir Karajovic”, Deligradska 29, 11000 Belgrade, Serbia;2. Singidunum University, Faculty of Applied Ecology (FUTURA), Pozeska 83a, 11000 Belgrade, Serbia;3. Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia;1. Radiation Dosimetry Laboratory, Department of Medical Physics, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India;2. Plant Genetic Engineering Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India;3. Department of Medical Physics, Bharathidasan University, Trichirapalli 620 024, Tamil Nadu, India;1. Homi Bhabha National Institute, Anushakthi Nagar, Mumbai, India;2. Water and Steam Chemistry Division, Bhabha Atomic Research Centre (F), Kalpakkam, Tamilnadu, India;3. Radiological and Environment Safety Division, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamilnadu, India |
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| Abstract: | Human population variability to standardized doses of N-acetoxy-2-acetylaminofluorene (NA-AAF) and 7,12-dimenthylbenz(a)anthracene (DMBA) was determined in cultured lymphocytes by measuring (a) differential stimulation of unscheduled DNA synthesis after 1 h induction of DNA damage by 10 μM NA-AAF, (b) the level of NA-AAF induced chromosome aberrations remaining after 8 h of DNA-repair synthesis, and (c) the level of [3H]DMBA bound to DNA after 18 h incubation of resting lymphocytes in 5 μM DMBA. All 3 parameters indicated individual variation to carcinogen exposure and were correlated to the population differences in age, sex, blood pressure and mortality rates. Males always had a greater potential to accumulate DNA-damage than did females regardless of the sampled population. DNA-damage potentials increased with increasing age, blood pressure of mortality rates. There was always proportionally greater DNA-damage potentials in the males than in females. The in vitro response of mature granulocytes to a 10 μM NA-AAF dose, as estimated by [3H]thymidine incorporation from unscheduled DNA synthesis, was much lower than lymphocyte response. Nevertheless, individual variations in granulocyte NA-AAF induced unscheduled DNA synthesis paralleled the inter-individual fluctuations observed in the lymphocyte responses to NA-AAF. |
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