Transplacental mutagenicity of N‐ethyl‐N‐nitrosourea at the hprt locus in T‐lymphocytes of exposed B6C3F1 mice

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Abstract
Previous studies have compared age‐related differences in total mutagenic burden in mice of differing age (preweanling, weanling, or young adult) after single intraperitoneal (i.p.) injections of ethylnitrosourea (ENU). The purpose of the present investigation was to determine the effects of time elapsed since treatment on the frequency of hprt mutant T‐cells (Mf) from mice treated transplacentally with single acute vs. multiple split doses of ENU. To this end, pregnant C57BL/6 mice (n = 13–16/group), which had been bred to C3H males, were given i.p. injections of 40 mg ENU/kg bw in a single dose on day 18 of gestation, in a split dose of 6 mg ENU/kg bw on days 12 through 18 of gestation, or DMSO vehicle alone. Groups of pups were necropsied on days 10, 13, 15 (single dose only), 17, 20, 40, and 70 postpartum for T‐cell isolations and hprt Mf measurements using the T‐cell cloning assay. The time required to reach maximum Mfs in T‐cells isolated from thymus of transplacentally treated animals was 2 weeks, the same time span as previously observed after ENU treatment of adult, weanling, and preweanling mice. Mfs in T‐cells isolated from spleens of control animals averaged 2.1 ± 0.3 (SE) × 10−6. In spleens of mice treated transplacentally with ENU in a single dose, Mfs reached a maximum at 15 days postpartum [84.7 ± 15.8 (SE) × 10−6] and decreased to lower but still elevated levels at 40 days postpartum. In spleens of mice treated transplacentally with ENU in a split dose, Mfs reached a maximum at 13 days postpartum [74.0 ± 16.3 (SE) × 10−6] and decreased to background levels at 40 days postpartum. The areas under the curves describing the change in hprt Mfs over time for ENU‐treated vs. control mice estimate the mutagenic potency for transplacental single‐ and split‐dose exposures to be 1.9 and 0.8 × 103, respectively. Comparison of the mutagenic potency estimates for mice exposed to ENU in utero to 4‐week‐old mice given a similar dose of the same lot number of ENU indicates that the mouse is more susceptible to ENU‐induced mutagenesis during fetal life. Environ. Mol. Mutagen. 38:30–37, 2001

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