Repair replication characteristics of human cells exposed to 1'-acetoxysafrole or 1'-acetoxyestragole.

Abstract

The response of cultured human cells to treatment with 1'-acetoxysafrole (1'-AcO-S) and 1'-acetoxyestragole (1'-AcO-E), which are electrophilic and mutagenic, has been examined. Fifty percent survival of T98G cells followed exposure to 0.2 mM 1'-AcO-E. Fifty percent inhibition of DNA synthesis rate occurred after exposure to 0.3-0.5 mM of either compound. DNA repair replication in treated cells was measured by the combined 5-bromodeoxyuridine density and radioisotope labelling method. Detectable levels of repair over a 4 h time period appeared following exposure to 0.1 mM or higher concentrations of either compound. However, the maximum level of repair in 1'-AcO-S-treated cells was only 15% of the value seen after a saturating dose of u.v. (254 nm), and that for 1'-AcO-E was only 10% of the u.v. maximum. The time course for repair was similar for u.v. and 1'-AcO-S up to at least 11 h after treatment. Normal human fibroblasts (GM38) exhibited a similar ability to that of T98G cells for repair of 1'-AcO-S-induced damage. Even SV40-transformed fibroblasts from a xeroderma pigmentosum patient (complementation group A) exhibited a low but significant amount of repair after treatment with 0.5 mM 1'-AcO-S. The repair patch size distribution in T98G cells treated wih 1'-AcO-S or 1'-AcO-E was 19-23 nucleotides, -70% of the value obtained by the density-labelling method in u.v.-irradiated human cells.