Open Access3 H‐5‐IODO‐2′‐DEOXYURIDINE TOXICITY PROBLEMS IN CELL PROLIFERATION STUDIES
Author(s) -
Dethlefsen Lyle A.
Publication year - 1974
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.1974.tb00901.x
Subject(s) - deoxyuridine , toxicity , idoxuridine , thymidine , ratón , tritium , mole , chemistry , mitotic index , ethanol , microbiology and biotechnology , carcinogen , dna , biochemistry , pharmacology , biology , endocrinology , mitosis , immunology , virus , physics , organic chemistry , nuclear physics
The toxicity of 3 H‐5‐iodo‐2′‐deoxyuridine ( 3 H‐IUdR) was evaluated by injecting tumor‐bearing C3H mice with different concentrations of ethanol (the solvent), different doses of tritium tagged onto either IUdR or thymidine and different chemical doses of IUdR, and then measuring the 3 H‐IUdR incorporation into duodenal and mammary tumor DNA as well as the cellular kinetics of duodenal crypt cells. Ethanol (37% or less, 0.2 ml/mouse) does not significantly inhibit IUdR incorporation into DNA, and the incorporation after a tritium dose of 75 μCi 3 H‐IUdR/mouse (about 3 μCi/g body weight) is not less than the incorporation following an injection of 25 μCi 3 H‐IUdR/mouse when the IUdR dose is below 0.005 μmole per mouse. The toxic effects are primarily due to chemical toxicity from IUdR per se. IUdR, at doses of 0.2 μmoles per mouse does inhibit IUdR incorporation into duodenal and tumor DNA, and the duodenal labeling index and the fraction of labeled mitoses are significantly reduced when 0.013 μmole IUdR per mouse is injected. Also some of the duodenal cells containing IUdR apparently undergo only one post‐labeling division and the generation time (T c ) of the cells containing IUdR (25 μCi 3 H‐IUdR/mouse) is 15.3 hr as compared to 13.3 hr for cells labeled with 3 H‐T (75 μCi/mouse). This increase in T c is probably not statistically significant; nevertheless, these results do indicate that one must be exceedingly cautious when using 3 H‐IUdR as a radiotracer for studies concerned with in vivo cellular kinetics and, at least for C3H mice, the dose should be less than 0.01 μmole per 25 g mouse.