Increased bystander mutagenic effect in DNA double-strand break repair-deficient mammalian cells

• Published in: International journal of radiation biology Vol. 79; no. 1; pp. 35 - 41
• Main Authors: Nagasawa, H., Huo, L., Little, J. B.
• Format: Journal Article
• Language: English
• Published: London Informa UK Ltd 2003; Taylor & Francis
• Subjects: Alpha Particles; Animals; Biological and medical sciences; Bystander Effect; CHO Cells; Cricetinae; DNA Damage; DNA Repair; Medical sciences; Mutation
• ISSN: 0955-3002; 1362-3095
• DOI: 10.1080/0955300021000019230

Purpose : We have shown previously that when monolayer cultures of Chinese hamster ovary (CHO) cells are exposed to very low fluences of alpha-particles, HPRT mutations are induced in non-irradiated 'bystander' cells in the population. The present investigation was designed to examine the role of DNA repair in this process. Materials and methods : The DNA double-strand repair-deficient mutant cell line xrs-5 was exposed to mean doses of alpha-particles as low as 0.04 cGy whereby less than 1% of the nuclei were traversed by an alpha track and thus received any radiation exposure. Results : With this very low alpha-particle fluence, most of the cells in the xrs-5 population appeared to be at risk for the induction of mutations, indicating a much larger bystander effect than observed with wild-type CHO cells. Molecular structural analyses showed that xrs-5 mutants primarily involved partial and total gene deletions as opposed to wild-type cells where point mutations predominated in bystander cells. Conclusions : These results indicate a very large bystander effect in xrs-5 cells. They support the hypothesis that unrepaired or misrepaired double-strand breaks (DSB), arising from opposed DNA lesions, enhance the sensitivity of bystander cells in xrs-5 cultures to the induction of mutations.