Sensitization of Mouse L Cells to Ultraviolet Light by Low Amounts of Bromodeoxyuridine

Abstract

Substitution of bromouracil for at least 5% of the thymines in DNA of mouse L [L929] cells causes a maximum sensitization of 4- to 5-fold to killing by UV light. The substitution of bromouracil (by incubation of cells with bromodeoxyuridine) results in a net increase in the total number of lesions in DNA per unit dose of radiation, owing to the breaks associated with bromouracil photolysis. Estimates of critical target size from the D37 [mean in activation dose] indicate that the additional cytotoxicity caused by bromouracil substitution may be association with the production of a few breaks in large regions of DNA, suggesting that damage at the level of a chromosome aberration may be the lethal event. Dilution of bromouracil-substituted DNA by growth of cells in thymidine indicated that there was no difference between the sensitivity of cells substituted in one or both strands of DNA. The sensitivity decreased as the number of chromosomes containing bromouracil halved at each cell division and reached normal sensitivity when the number of divisions was sufficient to produce one or fewer substituted chromosomes per cell.