In utero sister chromatid exchange analysis for detection of transplacental mutagens

Kram, David; Bynum, Gaither D.; Senula, Gerhard C.; Schneider, Edward L.

doi:10.1038/279531a0

Cited by 35 publications

(10 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Erythrocytes from fetal blood were inspected for micronuclei after cyclophosphamide, DEN, mitomycin C, procarbazine, or trenimon treatment [King and Wild, 1979;Cole et al, 19821 of pregnant female mice or after DMN treatment of pregnant rats [Fumero et al, 19811. Finally, sister chromatid exchanges (SCEs) were used as indicators for a cytogenetic event in transplacentally treated embryos with the chemical mutagens adriamycin [Kram et al, 19791, BaP [Galloway et al, 19801, cyclophosphamide [Basler, 1979, 1980Kram et al, 1979;Allen et al, 19811, MMS [Basler, 1979, 19801, and mitomycin C [Kram et al, 19791.…”

Section: Introductionmentioning

confidence: 99%

New approaches to mutagenicity studies in animals for carcinogenic and mutagenic agents. II. Clastogenic effects determined in transplacentally treated mouse embryos

Adler¹

1983

Teratog. Carcinog. Mutagen.

View full text Add to dashboard Cite

Cell suspensions from whole embryos were obtained on the 12th day of gestation from treated pregnant female mice. For the present experiments five model mutagens-BaP, bleomycin, mitomycin C, procarbazine, and TEM--were chosen for their different modes of action in inducing chromosomal aberrations. Time-response and dose-response were studied for chromosomal aberrations induced by transplacental treatment of mouse embryos. All five known mutagens gave a positive response in the present system. The maximum time of response varied from compound to compound and was found as early as 3h after treatment with the G2-clastogen bleomycin or as late as 18 h after treatment with the bifunctional alkylating agent TEM. Chromatid breaks and exchanges increased with dose in all instances. The correlations between clastogenic, carcinogenic, and teratogenic effects are discussed. It is concluded that the transplacental cytogenetic test may be applicable to identify chemicals that exhibit all three properties.

show abstract

Section: Introductionmentioning

confidence: 99%

New approaches to mutagenicity studies in animals for carcinogenic and mutagenic agents. II. Clastogenic effects determined in transplacentally treated mouse embryos

Adler¹

1983

Teratog. Carcinog. Mutagen.

View full text Add to dashboard Cite

show abstract

“…Approaches for the detection of fetal DNA damage through the analysis of sister chromatid exchanges (SCE) in mouse fetal chromosomes have been described in recent reports (1)(2)(3). Operationally, SCE are reciprocal exchanges of fluorescent intensities between sister chromatids observed in metaphase cells that have replicated twice in the presence of bromodeoxyuridine.…”

mentioning

confidence: 99%

In utero analysis of sister chromatid exchange: alterations in suscptibility to mutagenic damage as a function of fetal cell type and gestational age.

Kram¹,

Bynum²,

Senula³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Frequencies of baseline and cyclophosphamide-induced sister chromatid exchanges (SCE) were measured in mouse maternal and fetal cells between days 11 and 19 of gestation. Baseline levels of SCE did not vary as a function of gestational age in either the mother or fetus. Cyclophosphamide-induced SCE frequencies remained constant in maternal cells but declined dramatically in the fetus throughout the latter half of development. Because cyclophosphamide is a metabolically activated mutagen, a direct-acting drug, mitomycin C, was given on days 11 and 15 to determine if the decline in induced SCE levels seen with gestational results from alterations in activating enzymes. A similar decline in mitomycin C-induced SCE levels was noted in fetal tissues as a function of gestational age. Dose-response curves to cyclophosphamide performed on day 13 of gestation showed increases in SCE as a function of cyclophosphamide concentration in both the mother and the fetus. When mutagen-induced SCE levels were compared in different fetal organs, the direct-acting drugs (mitomycin C and daunomycin) were found to induce similar levels in all tissues. Cyclophosphamide, which is metabolically activated, induced higher SCE levels in fetal liver than in lung or gut. Whereas cyclophosphamide induced similar SCE levels in fetal and maternal cells on day 13 of gestation, daunomycin produced fetal SCE levels that were approximately 50% of maternal levels. Simultaneous measurement of the distribution of [14C]cyclophosphamide and [3H]daunomycin in maternal and fetal cells revealed that the lower SCE induction by daunomycin was probably due to decreased ability to cross the placental barrier.

show abstract

“…1976;Vogel and Bauknecht. 1976;Allen et al, 1977) in order to screen for genotoxic effects in specific target tissues and organs (Allen et al 1976;Conner et al 1979: Kram et al 1979a. especial ly in circulating peripheral lymphocytes (Klingerman et al 1981;Crossen.…”

mentioning

confidence: 99%

A comparison of sister chromatid exchange frequencies in peripheral lymphocytes and bone marrow cells of Fischer 344 and Sprague-Dawley rats

Dearfield¹,

Jacobson‐Kram²,

Williams³

1984

Cytogenet Genome Res

View full text Add to dashboard Cite

We have investigated spontaneous sister chromatid exchange (SCE) frequencies in peripheral lymphocytes and bone marrow cells explanted from two strains of the laboratory rat, Fischer 344 and Sprague-Dawley. A small, but significant difference was noted for both cell types, with the Fischer 344 rat being consistently higher. Other cell parameters, such as the mitotic index and the replicative index, were similar in the two strains. SCE levels in cultured peripheral lymphocytes after intraperitoneal administration of the alkylating drug cyclophosphamide (10 mg/kg) were similar for the two strains. Fischer 344 rats are known to have approximately a 10-fold higher incidence of spontaneous leukemia than do Sprague-Dawley rats. Since SCE frequency is a sensitive measure of DNA damage, our observations suggest that high leukemia incidence in the Fischer 344 rat may be related to a higher level of spontaneous DNA damage.

show abstract

In utero sister chromatid exchange analysis for detection of transplacental mutagens

Cited by 35 publications

References 12 publications

New approaches to mutagenicity studies in animals for carcinogenic and mutagenic agents. II. Clastogenic effects determined in transplacentally treated mouse embryos

New approaches to mutagenicity studies in animals for carcinogenic and mutagenic agents. II. Clastogenic effects determined in transplacentally treated mouse embryos

In utero analysis of sister chromatid exchange: alterations in suscptibility to mutagenic damage as a function of fetal cell type and gestational age.

A comparison of sister chromatid exchange frequencies in peripheral lymphocytes and bone marrow cells of Fischer 344 and Sprague-Dawley rats

Contact Info

Product

Resources

About