EFFECTS OF THYMIDINE ANALOGUES ON MURINE AND HUMAN CELLS

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Abstract
Three mouse tumour cell lines grew continuously in 3 M 5-bromodcoxyuridine (BUdR). One line (MC-2) produced a retrovirus and altered in morphology in the presence of BUdR or 5-iododeoxyuridine (IUdR). These effects, which could be reversed by growth in normal medium, were similar to those reported for the B-16 mouse melanoma line. The B-16 line used in this study, however, as well as a variety of human cells (six melanoma lines and three fibroblast strains), were much more sensitive to BUdR, 003–01 M being the maximum tolerated levels for continuous growth. No virus production or changes in morphology were induced in these cells by BUdR, deoxyuridine (UdR), 5-fluorodcsoxyuridine (FUdR) or thymidine (TdR). The results of cell labelling and growth studies showed a correlation of Incorporation of BUdR into DNA with toxicity. Compared on a competitive basis with 1 M TdR, the order of incorporation of 1 M nucleosides by two human cell lines was TdR = BUdR = 1UdR UdR FUdR. In contrast to previous reports that FUdR is incorporated into RNA but not into DNA, half of the FUdR label was found in alkali-stable, DNase-sensitive material. Over 90% of the other compounds was incorporated into DNA. All of the UdR and 60% of the 1UdR label was incorporated as thymidine: this conversion could be inhibited by labelling in the presence of FUdR.

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