Impact of long-term exposure to sodium arsenite on cytogenetic radiation damage.
The aim of this work was to investigate the impact of long-term exposure to low concentrations of sodium arsenite on the cellular response to ionising radiation. Human lymphoblastoid GM1899a cells were cultured in the presence of sodium arsenite for up to six months. Following chemical exposure, acute challenge doses of X-rays were given and chromosome damage (dicentrics, acentric fragments, translocations, micronuclei) as well as cell growth and changes in cell cycle kinetics were determined. Initial short-term chemical exposures determined 8 ng/ml (60 nM) sodium arsenite as a suitable concentration for chronic exposures, which is below the current World Health Organization limit for arsenic in drinking water. At this concentration, cell growth was slightly, but consistently, slower than in untreated cultures throughout the six-month exposure period. Long-term exposure to the chemical induced no dicentrics and did not significantly alter the yield of dicentrics induced by 1 Gy acute X-irradiation. Similar results were obtained for chromosome translocations. In contrast, exposure to 8 ng/ml sodium arsenite induced significant levels of acentric fragments and micronuclei. Fragment/micronuclei data in combined treatment samples compared with single treatments were consistent with an additive effect of chemical and radiation exposure. As for X-rays, micronuclei induced by sodium arsenite tended to show no centromere in situ hybridisation signal, indicating that they represent structural aberrations rather than mis-segregated chromosomes. Similar results were obtained in human peripheral lymphocytes following short-term exposure to sodium arsenite or X-rays. Overall, an additive effect was observed for all combined exposures. Cellular radiation responses therefore seem to operate without any modulatory effects from chronic low level exposure to sodium arsenite in the systems analysed here.
Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon, OX11 0RQ, UK.
Otilia
O
Nuta
Jayne
J
Moquet
Simon
S
Bouffler
David
D
Lloyd
Ovnair
O
Sepai
Kai
K
Rothkamm
D018053:Arsenites / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000187:drug effects* / Q000528:radiation effects*; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016014:Linear Models; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D017670:Sodium Compounds / Q000633:toxicity*
D018053:Arsenites; D017670:Sodium Compounds; C017947:sodium arsenite