Radioprotection of Cultured Mammalian Cells by the Aminothiols WR-1065 and WR-255591: Correlation between Protection against DNA Double-Strand Breaks and Cell Killing after γ Radiation

Abstract

We compared the effects of the radioprotective aminothiols WR-1065 and WR-255591 on the induction of DNA double-strand breaks (DSBs) and on the survival of aerated Chinese hamster ovary cells exposed to 60Co gamma radiation. DSBs were measured using the pH 9.6 neutral elution method. In agreement with earlier studies, protection factors for both drugs measured using the end point of clonogenic cell survival were significantly greater than the protection factors for DSB induction when DSBs were measured after gamma-ray doses ranging from 20 to 90 Gy. However, when DSBs and cell survival measurements were made on the same cell populations after low radiation doses (between 3 and 30 Gy) using the replicate plating method, there appeared to be a close correlation between the modification of DSB induction and the modification of cell survival produced by both drugs. The major influence accounting for the differences between these and previously obtained results appears to be the range of radiation doses used, suggesting that protection against DSB induction is radiation-dose dependent.

In Vitro Studies with Methylproamine

“…In a cell culture experiment with Chinese hamster ovary cells, comparable with the methylproamine experiments described here, a dose-modifying factor of 1.9 was reported for 4 mM WR1065 (17). A more recent article reported a dose-modifying factor of 1.5 for radioprotection of V79 cells by 4 mM WR1065 (18).…”

A Comparison of Kinetic Photon Cell Survival Models

“…This correlation has been found experimentally by several groups (10)(11)(12)(13) and these correlations support the reasoning presented in the first molecular theory publication (3) and in the book ''The Molecular Theory of Radiation Biology'' (5).…”

Aminothiols Linked to Quinoline and Acridine Chromophores Efficiently Decrease 7,8-dihydro-8-oxo-2′-deoxyguanosine Formation in γ-irradiated DNA

“…Similarly the extent of adenine, guanine and thymine release from DNA upon steady-state radiolysis of aerated aqueous solutions was found to strongly depend on the charge of the thiols (Zheng et al . 1988), the maximum protection being observed with WR-1065 (Z+2) (Murray et al . 1989, Tahsildar et al .…”