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EFFECTS OF THYMIDINE ANALOGUES ON MURINE AND HUMAN CELLS
Author(s) -
Smellie SG,
Parsons PG
Publication year - 1979
Publication title -
australian journal of experimental biology and medical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0004-945X
DOI - 10.1038/icb.1979.58
Subject(s) - thymidine , bromodeoxyuridine , cell culture , deoxyuridine , microbiology and biotechnology , biology , dna , dna synthesis , retrovirus , biochemistry , cell growth , chemistry , genetics
Summary Three mouse tumour cell lines grew continuously in 3 μM 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, 0·03–0·1 μM 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 μM TdR, the order of incorporation of 1 μM 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.