Low dose radiation-induced adaptive response preventing HPRT mutation is Fhit independent.
OBJECTIVE
To study whether fragile histidine triad (Fhit) prevents IR-induced hypoxanthineguanine phosphoribosyltransferase (HPRT) mutation and whether Fhit plays any role in preventing HPRT mutation through low dose-induced adaptive response.


METHODS
Establishing human cell lines with or without Fhit expression by making constructs expressing hemagglutinin (HA) alone or HA-Fhit fusion protein and transfecting the vector to HeLa cells. The effects of Fhit on ionising radiation (IR)-induced mutation were examined by observing HPRT mutation rates in the established cell lines following different doses of IR. The role of Fhit on low dose IR-induced adaptive response were examined by observing HPRT mutation rates in the established cell lines that were exposed to 0.1 Gy and followed with high dose IR or ultraviolet (UV) exposure.


RESULTS
Low dose (0.1 Gy) does not affect HPRT mutation rates in these cell lines. Fhit prevents high dose IR (> or = 2 Gy)-induced mutation as it prevents UV-induced mutation. However, low dose of IR (0.1 Gy)-induced adaptive response prevents both high doses of IR and UV-induced mutation in both the cells with and without Fhit expression.


CONCLUSIONS
Fhit prevents IR-induced HPRT mutation and preventing mutation through low dose of IR-induced adaptive response is Fhit independent.
Lu
Lin
L
Department of Radiation Oncology, Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Hu
Baocheng
B
Yu
Fang
F
Wang
Ya
Y
D017766:Acid Anhydride Hydrolases / Q000235:genetics / Q000378:metabolism*; D000222:Adaptation, Physiological / Q000235:genetics* / Q000528:radiation effects*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D009154:Mutation / Q000528:radiation effects*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D006388:Hemagglutinins; D007041:Hypoxanthine Phosphoribosyltransferase; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase