Mutagenesis and lethality following S phase irradiation of xeroderma pigmentosum and normal human diploid fibroblasts with ultraviolet light

Abstract

The mutagenic and lethal effects of u.v. light exposure in the DNA synthetic phase of the cell cycle were determined in xeroderma pigmentosum complementation group A (XP-A), hereditary adenomatosis of the colon and rectum (ACR), and a normal, foreskin derived cell strain (AG1522). For AG1522, an increased sensitivity to the cytotoxic effects of u.v. light (survival curve D ₀ = 3.2 J/m ² ) was observed as compared to previous findings for confluent, non-proliferating cultures (D ₀ = 4.2 J/m ² ). XP-A fibroblasts were markedly hypersensitive (D ₀ = 0.5 J/m ² ) and ACR fibroblasts exhibited an intermediate response (D ₀ = 2.0 J/m ² ). The mutagenic response of ACR fibroblasts, however, was similar to normal fibroblasts. A threshold of 1.5–2 J/m ² was observed for u.v. induced mutagenesis in normal and ACR fibroblasts. XP fibroblasts, on the other hand, were strikingly hypermutable and demonstrated little or no threshold. When S phase mutagenesis was considered as a function of survival level rather than u.v. light dose, XP fibroblasts remained significantly hypermutable as compared with normal fibroblasts at all survival levels. Previous mutagenesis results with confluent, nonproliferating cultures of XP and normal fibroblasts were reanalyzed as a function of cytotoxicity; XP hypermutability at all survival levels was also observed.