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


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.
Nagasawa
H
H
Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Huo
L
L
Little
J B
JB
D000512:Alpha Particles; D000818:Animals; D024201:Bystander Effect; D016466:CHO Cells; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D009154:Mutation