RADIATION-INDUCED LONG-LIVED RADICALS WHICH CAUSE MUTATION AND TRANSFORMATION

Using electronic spin resonance (ESR), we found a new type of radical with a long life-time in cells (T-1/2 > 20 h) and which may play a mor e important role in the induction of mutation and transformation than either the active, short-lived, H, or OH radicals. When cells were tre ated with dimethyl sulfoxide (DMSO) and L-ascorbic acid (AsA) just bef ore irradiation, the short-lived radicals were well-scavenged. On the other hand, if cells were treated with the scavengers 20 min after irr adiation, then AsA scavenged the long-lived radicals, but DMSO did not . AsA treatment 20 min after the start of irradiation drastically redu ced both the frequencies of mutation at the hypoxanthine guanine phosp horibosyl transferase (HGPRT) locus in human cells and morphological t ransformations in mouse m5S cells, but DMSO treatment did not. In addi tion, AsA treatment 20 h after irradiation also reduced the mutation f requency in human cells. These results suggested that mutations and mo rphological transformation are probably caused by the presence of long -lived radicals in the cells, rather than by short lived radicals, and that AsA reacts efficiently with long-lived radicals, resulting in a decrease of the mutations and transformations induced. (C) 1998 Elsevi er Science B.V. All rights reserved.