Decreased deletion mutation in radioadapted human lymphoblasts

Area of Science:

• Radiobiology
• Molecular Biology
• Genetics

Background:

• Low doses of ionizing radiation can sometimes induce resistance to subsequent higher doses.
• The mechanisms underlying radioadaptive responses, particularly at the molecular level, require further elucidation.

Purpose of the Study:

• To investigate the effect of low-dose gamma ray preexposure on the mutagenic response to a high dose in human lymphoblastoid cells.
• To characterize the molecular nature of mutations induced by high-dose gamma rays with and without prior low-dose adaptation.

Main Methods:

• Human lymphoblastoid cells were exposed to a low dose (0.02 Gy) of gamma rays followed by a high dose (4.0 Gy) or only the high dose.
• Cell survival and hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutant frequency were assessed.
• Southern hybridization analysis was used to determine the molecular alterations in HPRT mutants.

Main Results:

• Low-dose preexposure reduced HPRT mutant frequency by 70% compared to the high dose alone, with no significant effect on cell survival.
• The proportion of HPRT mutants with detectable gene alterations decreased from 78% (high dose alone) to 42% (low-dose preexposed).
• The fraction of mutants with partial HPRT gene deletions was significantly lower in the adapted group (19%) compared to the non-adapted group (52%).

Conclusions:

• Low-dose gamma ray preexposure confers resistance to the mutagenic effects of a high dose in human cells.
• This adaptation is associated with a shift in mutational specificity, favoring mutations with fewer or no HPRT gene alterations.
• The findings suggest the induction of an error-free DNA repair mechanism that preferentially repairs deletion-prone lesions.