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Mutation induction by charged particles of defined linear energy transfer
T K Hei1, D J Chen, D J Brenner
1Radiological Research Laboratories, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
Carcinogenesis
|July 1, 1988
Summary
High-energy charged particles, or high-linear energy transfer (LET) radiation, are more effective at causing mutations in human cells than lower-LET radiation like gamma-rays. This finding has implications for understanding radiation mutagenesis.
Area of Science:
- Radiation Biology
- Molecular Toxicology
- Genetics
Background:
- The mutagenic effects of ionizing radiation are dependent on its linear energy transfer (LET).
- Understanding the mutagenic potential of different radiation types is crucial for risk assessment.
Purpose of the Study:
- To assess the mutagenic potential of charged particles with defined LET using the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in primary human fibroblasts.
- To compare the mutation rates induced by charged particles with those induced by 137Cs gamma-rays.
Main Methods:
- Primary human fibroblasts were irradiated with protons, deuterons, or helium-3 ions at varying LETs (10-150 keV/micron).
- Cell survival and 6-thioguanine resistance (a measure of mutation) were assayed post-irradiation.
- Mutation rates were compared between high-LET charged particles and low-LET 137Cs gamma-rays.
Main Results:
- Mutation frequencies showed a direct correlation with LET.
- The relative biological effectiveness (RBE) for mutagenesis ranged from 1.30 to 9.40, increasing with LET.
- High-LET radiations were more efficient mutagens than low-LET gamma-rays.
Conclusions:
- High-LET charged particles are significantly more effective at inducing mutations in human fibroblasts compared to low-LET gamma-rays.
- These findings are consistent with previous studies on both rodent and human cell lines.
- The data highlight the potent mutagenic capacity of high-LET radiation, in addition to its cell-killing efficiency.