The distribution and fate of bromodeoxyuridine and bromodeoxycytidine in the mouse and rat.

Abstract

Summary Bromodeoxyuridine (BudR) was rapidly and extensively degraded in vivo in the rat, with the concomitant formationof bromouracil and bromide ion. The liver is a major site of dehalogenation. A portion of the administered compound escaped degradation and was incorporated into the DNA of various tissues in a pattern similar to that of thymidine incorporation. In the rat, bromodeoxycytidine (BCdR) was more slowly degraded than BUdR. Neither bromocytosine nor bromouracil could be detected as degradation products. Following administration of BCdR-Br82, the distribution of Br82 activity in the DNA of various organs was different from that which followed injection of BUdR-Br82. Some evidence was presented which suggests that such a difference may be due to deoxycytidylate deaminase activity in particular tissues, such as the bone marrow. Following incorporation of Br82 by Ehrlich ascites cells after intraperitoneal administration of BUdR-Br82 or BCdR-Br82 to mice, the radioactive label was conserved during neoplastic cellular multiplication for at least four successive generations. Ehrlich ascites cells, exposed in vivo to repeated intraperitoneal injections of BUdR and subsequently irradiated with 350 r, showed a greater inhibition of their post-treatment growth curves in vivo than did irradiated cells not exposed to BUdR.