Bromodeoxyuridine inhibition of Friend leukemia cell induction. Mechanism of reversal by deoxycytidine

Deoxycytidine (dC) reverses bromodeoxyuridine (brdUrd) inhibition of induction in Friend leukemia cells only if added within the first 6 h after the addition of brdUrd. dC is shown to reduce the uptake of [3H]brdUrd into both soluble nucleotide pools and DNA, substantially expand the dTTP pool, and result in a lower level of brdUrd substitution in DNA. When the conversion of dC to thymidine nucleotides is prevented in BATH medium (containing brdUrd, aminopterin, thymidine, and hypoxanthine), dC no longer reverses brdUrd inhibition. These results show that dC exerts its primary effect via alterations in thymidine pools and probably through the resultant lower substitution of brdUrd in DNA.