Inhibitory effect of folinic acid on radiation-induced micronuclei and chromosomal aberrations in V79 cells.
Folinic acid (FA), clinically called leucovorin, has been widely used as a nutrient supplement in dietary intake and is capable of inhibiting cytotoxicity and chromosomal damage induced by chemicals. However, data on its antigenotoxic effect on radiation-induced chromosomal damage are limited. The present study was, therefore, performed to investigate the effect of FA on radiation-induced (X-rays and UV radiation) micronuclei (MN) and structural chromosomal aberrations (SCA) concurrently in V79 Chinese hamster lung cells. Exponentially growing cells were exposed to five doses of X-rays (1-12 Gy) and UV radiation (50-800 microJ x 10(2)/cm2) and post-treated with 5 or 50 micrograms FA/ml of culture medium for 16 h. The slides were analyzed for the presence of MN and SCA using standard procedures. The results showed that X-ray treatment alone produced dose-related cytotoxicity as measured by nuclear division index (NDI) and mitotic index (MI). X-rays produced a clear dose-related clastogenicity as measured by percent of micronucleated binucleated cells (MNBN) (5-79%) and percent of aberrant cells (11-92%). FA at 5 micrograms/ml slightly decreased X-ray induced chromosomal damage in both assays; however, the inhibition was significant (12-46% of MNBN, 14-48% in aberrant cells) only when X-ray-treated cultures were post-treated with 50 micrograms FA/ml. Post-treatment of FA had no effect on X-ray induced cytotoxicity as measured by NDI and MI. A similar a dose-related increase in % MNBN (0.5-10.3%) and percent aberrant cells (6-35%) was produced by UV radiation treatment alone. There were significant percentages of MNBN and aberrant cell inhibitions at both 5 and 50 micrograms/ml in both assays. As in the case of X-ray-treated cells, there was a clear dose-related cytotoxicity in UV-treated cells alone. No reduction in NDI or MI was found when UV-exposed cells were post-treated with 5 or 50 micrograms of FA. These data demonstrate the beneficial effect of FA in decreasing radiation-induced chromosomal damage.
Keshava
C
C
Genetics and Developmental Biology Program, College of Agriculture and Forestry, West Virginia University, Morgantown 26506-6108, USA.
Nagalakshmi
R
R
Ong
T
T
Nath
J
J
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D002955:Leucovorin / Q000494:pharmacology*; D008168:Lung / Q000528:radiation effects; D048629:Micronuclei, Chromosome-Defective; D009152:Mutagenicity Tests; D011836:Radiation Tolerance; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays; D014965:X-Rays
D011837:Radiation-Protective Agents; D002955:Leucovorin