Sister chromatid exchange in vivo in mice: I. The influence of increasing doses of bromodeoxyuridine

Wilmer, James L.; Soares, E.R.

doi:10.1002/em.2860020106

Cited by 12 publications

References 34 publications

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Characterization of a rat lymphocyte culture system for assessing sister chromatid exchange. II. Effects of 5‐bromodeoxyuridine concentration, number of white blood cells in the inoculum, and inoculum volume

1982

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We have examined the effects of variation in 5-bromodeoxyuridine (BrdU) concentration, the number of white blood cells (WBCs) in the inoculum, and inoculum volume on sister chromatid exchange (SCE) frequency, mitotic activity, and cell cycle kinetics of phytohemagglutinin-stimulated rat lymphocytes in whole blood culture. BrdU (1 to 5 microM) caused a dose-dependent increase in SCEs/metaphase (7.6 to 12.0) and a dose-dependent decrease in mitotic activity (5.3 to 3.1%). With 2 microM BrdU, as the number of cells in the inoculum increased (0.25 x 10(6) to 2.5 x 10(6)), the mitotic activity decreased (7.7 to 1.8%). At all BrdU concentrations examined, changes in the number of WBCs in the inoculum caused significant changes in the SCE frequency. Thus, high concentrations of BrdU do not stabilize the SCE frequency in the rat lymphocyte culture system. However, high BrdU concentrations (greater than or equal to 25 microM) did affect adversely the cells in culture as evidence by increased chromosome breakage, poor chromosome spreading and morphology, and up to an 8-fold reduction in mitotic activity. At BrdU concentrations greater than or equal to 33 microM, the mitotic indices were depressed (2.4 - 0.7%) at all WBC concentrations, and cell cycle delay was evident. Inoculum volumes greater than or equal to 0.4 ml, necessitated by low WBC counts in the animals, resulted in reduced mitotic activity and in some cases culture failure. Thus, we recommend the use of 2 microM BrdU and the addition of 1 x 10(6) WBCs/2 ml culture from animals with WBC counts ranging from 4-7 10(6)/ml to ensure adequate mitotic activity and stable baseline SCE frequencies.

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Characterization of a rat lymphocyte culture system for assessing sister chromatid exchange. II. Effects of 5‐bromodeoxyuridine concentration, number of white blood cells in the inoculum, and inoculum volume

1982

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The mutagenic activity of 5‐bromo‐2′‐deoxyuridine (BrdU) in vivo in rats

1983

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BrdU tablets were implanted subcutaneously in rats, and BrdU concentrations were determined in the serum. Within 5 hr peak concentrations of 10 micrograms BrdU/ml blood were reached. The influence of BrdU in vivo on cell cycling, DNA synthesis, spontaneous sister chromatid exchange (SCE) frequencies, and gene-mutation frequencies (6-TGr) was determined in freshly isolated cells from a subcutaneous granulation tissue. The most significant effect of BrdU in vivo was a doubling of the spontaneous 6-TGr frequency. In reconstruction experiments in vitro the mutagenic activity of BrdU applied in concentrations found in vivo was 2.5-6-fold higher. With the use of agar-coated tablets, BrdU concentrations in the blood were reduced by half, and no peak concentration was found. The differential staining of chromatids was still sufficient. Since the mutagenic effect of BrdU in vitro was found to be strongly concentration dependent, the use of agar-coated tablets is recommended in experiments in which the compound is used to demonstrate SCE in vivo.

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Genotoxic and embryotoxic effects of 5‐bromodeoxyuridine in the chick embryo

Novotná

Hubálek

Bednář

1994

Teratog Carcinog Mutagen

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Chick embryos were exposed intra-amniotically to the thymidine analog bromodeoxyuridine (BrdU) in order to study its embryotoxic and genotoxic effects. Teratogenic effects were observed at doses of BrdU which failed to produce mitotic inhibition, clastogenic effects or any significant increase in sister chromatid exchanges. Clastogenic effects and depressed cell proliferation were observed only at high embryolethal doses. Thus, BrdU-induced teratogenicity was independent of genotoxic effects manifested at chromosomal level. On the contrary, a significant increase of DNA single strand breaks was detected even 24 hours after the administration of teratogenic dose. BrdU incorporation in the DNA does not appear to prevent embryonic cells from mitotic proliferation. Whether the single strand breaks in DNA would ultimately lead to BrdU-induced teratogenesis in chick embryos remained undetermined.

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Sister chromatid exchange in vivo in mice: I. The influence of increasing doses of bromodeoxyuridine

Cited by 12 publications

References 34 publications

Characterization of a rat lymphocyte culture system for assessing sister chromatid exchange. II. Effects of 5‐bromodeoxyuridine concentration, number of white blood cells in the inoculum, and inoculum volume

Characterization of a rat lymphocyte culture system for assessing sister chromatid exchange. II. Effects of 5‐bromodeoxyuridine concentration, number of white blood cells in the inoculum, and inoculum volume

The mutagenic activity of 5‐bromo‐2′‐deoxyuridine (BrdU) in vivo in rats

Genotoxic and embryotoxic effects of 5‐bromodeoxyuridine in the chick embryo

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