PARENT SESSION
1:30 PM to 3:30 PM
Wednesday, April 24, 2002
Poster Session 30 Bystander Effects
Room: Nevada Exhibition Center
(P35-350) Bystander effects: Mutations and chromosomal aberrations in DNA repair deficient cells.
Little, John*,1, Nagasawa, Hatsumi1, 1 Harvard School of Public Health, 665 Huntington Avenue, Boston, MA
ABSTRACT-
Confluent cultures of CHO cells were exposed to very low fluences of Plutonium-238 alpha particles such that as few as 0.2-1.0% of the cells were traversed by a single particle, the remainder receiving no radiation exposure. In wild-type CHO cells, the frequency of HPRT mutations per nuclear traversal was increased 4-5-fold at low alpha particle fluences (1% cells hit), owing to mutations occurring in bystander cells. Molecular structural analyses indicated that >90% of these were point mutations, as compared with a preponderance of deletions among spontaneously arising and direct radiation-induced mutations. In the CHO derivative line xrs-5, which is deficient in DNA double strand break (DSB) repair, the mutation frequency per nuclear traversal increased >20-fold at low fluences (0.2% cells hit); in contrast to wild-type CHO cells, 80% of the mutations in xrs-5 bystander cells were partial or total gene deletions. The number of CHO cells with induced gross chromosomal aberrations per nucleus irradiated increased only 3-fold at low alpha particle fluences, indicating a small bystander effect, whereas it increased 15-fold in xrs-5 cells. Based on these observations, we hypothesize that mutations occurring in CHO bystander cells are a result of the enhanced oxidative stress occurring in these cells (Azzam et al, unpublished) that leads primarily to oxidative base damage and thus point mutations. The relatively small fraction of DSB induced in bystander CHO cells are efficiently repaired. In xrs-5 bystander cells, on the other hand, these breaks remain unrepaired leading to a high frequency of deletion mutants and gross chromosomal aberrations. In CHO bystander cells, where DSB are repaired and oxidative base damage predominates, few gross chromosomal aberrations are induced.
KEYWORDS: bystander effect , alpha radiation, mutagenesis, chromosomal aberrations