Short-term tests for transplacentally active carcinogens Sensitivity of the transplacental micronucleus test to diethylnitrosamine

Cole, R. J.; Taylor, Natalie; Cole, Jane; Henderson, L.M.; Arlett, C.F.

doi:10.1016/0165-7992(82)90139-7

Cited by 29 publications

(13 citation statements)

References 18 publications

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“…This eect of the compound as well as its perinatal genotoxicity (Cole et al 1982;Ning et al 1991) and hematotoxicity Snyder 1986, 1988;Corti and Snyder 1996) could be due, at least in part, to our observed perinatal bioactivation of the compound.…”

Section: Discussionmentioning

confidence: 61%

“…Our ®ndings of substantial perinatal benzene metabolism and bioactivation provide metabolic insights into the reported sensitivity of the immature to the toxic effects of the compound (Cole et al 1982;Ning et al 1991). The relative contributions of the enzymes involved in benzene bioactivation, e.g.…”

Section: Discussionmentioning

confidence: 97%

“…Of the few studies reported, some have judged benzene (Mehlman et al 1980) and its metabolites (DeCaprio 1999) to be of minimal hazard to the immature at doses that are nontoxic to the mother. Other studies, on the other hand, have demonstrated a higher genotoxicity by the compound, as estimated by micronucleus formation, in late fetuses of benzene-treated pregnant mice than in the dams themselves (Cole et al 1982(Cole et al , 1983Ning et al 1991;Xing et al 1992). Furthermore, ospring of benzene-treated pregnant mice were reported to exhibit abnormal hematopoiesis that persists into adulthood Snyder 1986, 1988;Corti and Snyder 1996).…”

Section: Introductionmentioning

confidence: 91%

“…Cellular macromolecules to which the resulting reactive benzene metabolites bind include DNA (Creek et al 1997) and protein (Irons and Neptun 1980;Chen and Eastmond 1995 ). Given the reported characteristically low levels of hepatic xenobiotic-bioactivation enzymes in the immature than in adults (Hong et al 1987;Umeno et al 1988) and the essentiality of metabolic bioactivation to benzene toxicity (Andrews et al 1977), the reported enhanced perinatal toxicity of benzene (Cole et al 1982(Cole et al , 1983Snyder 1986, 1988;Ning et al 1991;Xing et al 1992;Corti and Snyder 1996) raises the question of the relative contributions of the dam and the immature to the formation of the metabolites of benzene responsible for the perinatal toxicity.…”

Section: Introductionmentioning

confidence: 93%

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Comparative metabolism of [ 14 C]benzene to excretable products and bioactivation to DNA-binding derivatives in maternal and neonatal mice

Iba

Ghosal

Snyder

2001

Archives of Toxicology

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Lactating adult female mice treated with a single dose of 880 mg/kg i.p. [14C]benzene, and their 2-day-old sucklings similarly treated or nursed by their treated dams were compared in terms of their ability to metabolize benzene to urinary products or reactive intermediates as assessed by covalently-bound benzene derivatives in whole blood or liver DNA. Six metabolite fractions were identified in the urine of sucklings by high performance liquid chromatographic (HPLC) analysis at 5 h following intraperitoneal (direct) treatment with benzene. Three of the metabolite fractions co-chromatographed with authentic phenol, phenyl glucuronide, and muconic acid, and contributed 11, 6.9 and 0.6%, respectively, to the total urinary benzene metabolites. Two of the fractions were unidentified. The sixth and most polar fraction consisted of multiple metabolites, 21% of which were conjugates, and accounted for 72% of the total urinary metabolites. A similar metabolite profile was observed in 24-h urine samples from treated dams with the exception that one of the unidentified fractions in the sucklings was absent and levels of the metabolites were quantitatively higher than those observed in sucklings 5 h following their treatment with benzene. Furthermore, 78% of the most polar fraction from the dams consisted of conjugates compared with 21% of that from the sucklings. The metabolite pattern in urine of sucklings nursed by treated dams was qualitatively similar to, but quantitatively different from the pattern in treated dams. Five hours following intraperitoneal treatment with benzene, covalent binding of the compound to DNA (expressed as pmol benzene equivalents/mg DNA) in sucklings was slightly higher in whole blood (1.15+/-0.07) than in liver (0.77+/-0.07), whereas in the dam, it was slightly lower in whole blood (0.88+/-0.48) than in liver (1.63+/-0.61). Twenty four hours following benzene exposure in sucklings of benzene-treated dams, DNA binding by the compound in whole blood (3.85+/-1.05) and liver (0.11+/-0.03) was higher and lower, respectively than the binding observed in benzene-injected sucklings 5 h following the injection. Our results show that excretable as well as reactive metabolites of benzene are formed substantially by the neonatal mouse, and that the extent of bioactivation of the compound is comparable in the adult and the suckling mouse. The results show also that sucklings of benzene-exposed mothers are exposed to substantial levels of the compound and are potentially susceptible to its toxic effects.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 93%

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Comparative metabolism of [ 14 C]benzene to excretable products and bioactivation to DNA-binding derivatives in maternal and neonatal mice

Iba

Ghosal

Snyder

2001

Archives of Toxicology

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“…Micronucleus formation in maternal bone marrow is also analyzed for comparison. erable attention, with an increased focus on micronucleus formation in mouse fetal liver erythrocytes [Cole et al, 1979[Cole et al, , 1981[Cole et al, , 1982[Cole et al, , 1983Stoyel and Clark, 1980;Cihak and Vonterkova, 1987;Ciranni et al, 19881. The liver is the primary site of blood cell formation in the 0 1991 Wiley-Liss, Inc.…”

Section: Ntrod Uctl Onmentioning

confidence: 99%

Benzene‐induced micronuclei formation in mouse fetal liver blood, peripheral blood, and maternal bone marrow cells

Ning

Kado

Kuzmicky

et al. 1991

Environ and Mol Mutagen

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The transplacental cytogenetic effects of benzene were studied by using the micronucleus test of polychromatic erythrocytes (PCE) found in both fetal liver and fetal peripheral blood, and were compared with PCE from maternal bone marrow. Timed-pregnant mice received single intraperitoneal doses of benzene (0, 109, 219, 437, or 874 mg/kg bw) on the 14th day of gestation and were sacrificed 21 hr after injection. Benzene elicited a significant increase (P less than 0.01) in the frequency of micronucleated polychromatic erythrocytes (MNPCE) in fetal liver blood cells (0.55 to 1.36%, control 0.18%) at doses of 219 to 874 mg/kg, and in fetal peripheral blood cells (0.49 to 0.58%, control 0.25%) and maternal bone marrow cells (0.53 to 0.70%, control 0.10%) at doses of 437 and 874 mg/kg. The data demonstrate that benzene is a moderate transplacental clastogenic agent, and that the mouse transplacental micronucleus test using fetal liver blood cells is a potentially more sensitive indicator of the genotoxicity of benzene than either fetal peripheral blood or maternal bone marrow cells.

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Mutagenicity of cidial (phenthoate). I: Effect on maternal and fetal somatic cells

Nahas

Samad

Hondt

1997

Environ. Mol. Mutagen.

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Short-term tests for transplacentally active carcinogens Sensitivity of the transplacental micronucleus test to diethylnitrosamine

Cited by 29 publications

References 18 publications

Comparative metabolism of [ 14 C]benzene to excretable products and bioactivation to DNA-binding derivatives in maternal and neonatal mice

Comparative metabolism of [ 14 C]benzene to excretable products and bioactivation to DNA-binding derivatives in maternal and neonatal mice

Benzene‐induced micronuclei formation in mouse fetal liver blood, peripheral blood, and maternal bone marrow cells

Mutagenicity of cidial (phenthoate). I: Effect on maternal and fetal somatic cells

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