Treatment of patients with halogenated pyrimidines, in particular IUdR, has been found to increase tumor radiosensitivity. In mammalian cells, BUdR or IUdR pre-treatment increases their radiosensitivity in vitro. We have found that the initial level of DNA single strand and double strand breaks induced by x-rays in V79 rodent cells is increased in cells pre-treated with IUdR or BUdR. At clinically relevant doses, we have found that both DNA single strand breaks and DNA double strand breaks are increased approximately two-fold when 25% of the thymine bases are replaced with IUdR or BUdR. This level of substitution was obtained with a 10 uM dose of IUdR - a concentration which can be achieved in vivo.
