Human placenta does not Reduce AZT (zidovudine) to 3'-amino-3'-deoxythymidine

Human placental tissue and human trophoblast cells (JAr) were examined after exposure to the anti-HIV nucleoside analog AZT (Zidovudine) for the presence of 3'-amino-3'-deoxythymidine (AMT), a toxic catabolite. Placental cells were exposed to 7.6 mM AZT for 48 hr, and placental lobular tissue was perfused with 3.8 mM AZT for 14 hr. Cell homogenates were prepared, and supernatants were subjected to HPLC analysis. Despite large cellular concentrations of AZT, AMT was not detected in any of the samples analyzed. Exposure of JAr cells to this concentration of AZT produces a 72% inhibition of cell proliferation when compared with unexposed controls. Based upon the results of the current study, AMT was not formed by placental cells exposed to AZT and, thus, not a mechanism for toxicity after in vitro exposure to AZT.