Micronucleus formation by benzene, cyclophosphamide, benzo(a)pyrene, and benzidine in male, female, pregnant female, and fetal mice

Abstract

Male, female, pregnant female, and fetal ICR mice were compared for their acute sensitivity to four single doses of model carcinogens, as measured by micronucleus formation in polychromatic erythrocytes 24 h after treatment in adult bone marrow and fetal liver at days 17-19 of gestation. Cyclophosphamide caused a dose-responsive increase in micronuclei in all groups, without a consistent difference based on gender or pregnancy. At doses of 50 and 75 mg/kg given orally to the pregnant female, the fetuses were three to six times as sensitive as was the mother. Benzo(a)pyrene showed a similarly increased sensitivity of the fetus relative to the other groups, although it is a much weaker clastogen. Benzidine did not cause an increase in micronuclei in any group, although it was thought that the fetal liver might have been sensitive enough to detect it, relative to adult bone marrow. Benzene caused much less response in females than in males and almost no response in pregnant females and their fetuses, even though pregnant females metabolized at least half as much of the total dose as did the males (as measured by the presence of urinary metabolites of benzene). No single metabolite of benzene in the urine was consistently correlated with micronucleus formation in the bone marrow. Several factors must be interacting in different ways for different chemicals to influence their clastogenicity.

Seafood Contamination after the BP Gulf Oil Spill and Risks to Vulnerable Populations: A Critique of the FDA Risk Assessment

“…The FDA conducted a single risk assessment for adults and did not evaluate potential increased risks to the developing fetus or child, yet exposure to PAHs during pregnancy causes genetic damage to the developing fetus (Harper et al 1989; Orjuela et al 2010). Most PAHs are lipid soluble and therefore cross the placenta (Calabrese 1978; Shendrikova and Aleksandrov 1974).…”

Atsdr Evaluation of Health Effects of Chemicals. Iv. Polycyclic Aromatic Hydrocarbons (PAHs): Understanding a Complex Problem

“…An increased incidence of micronuclei in bone marrow cells harvested from the various groups of adult animals and also in the livers of the fetuses was observed (Harper et al, 1989). Genetic damage was most severe in the fetuses.…”

Biomarkers in Maternal and Newborn Blood Indicate Heightened Fetal Susceptibility to Procarcinogenic DNA Damage

“…In a number of rodent bioassays, fetal levels of PAH-DNA adducts have generally been higher than expected, given the lower estimated trans-placental dose of PAHs (Lu et al 1986; Lu and Wang 1990; Wang and Lu 1990). Similarly, levels of micronuclei formation and DNA single-strand breaks after transplacental PAH exposure have been shown experimentally to be higher in fetal than in paired maternal tissues (Bolognesi et al 1985; Harper et al 1989; Wang and Lu 1990). A previous study of a small number of maternal and cord blood samples from a Chinese population found comparable levels of PAH-DNA adducts measured by competitive enzyme-linked immunosorbent assay (ELISA) (Mumford et al 1993).…”