Variability of response to diethylstilbestrol: A comparison of inbred with hybrid mice

Abstract

The uterine and thymic weight responses to diethylstilbestrol (DES) were examined in BALB/cStCrlfC3Hf/Nctr, C57BL/6JfC3Hf/Nctr, C57BL/6 × BALB/c F ₁ hybrid (F₁), and monohybrid cross offspring (F₂) from the breeding of F ₁ mice. Weanling females were exposed for 6 d to dietary concentrations of DES of 2.5–1000 ppb (μg/kg feed). About 400 mice of each genetic population were used. In the uterine weight assay the slope of the dose‐response line was significantly less for the BALB/c than for the other populations. Uterine weight variances for the F ₁ hybrid and BALB/c mice were indistinguishable from each other and significantly smaller than variances for the F ₂ hybrid and C57BL/6 mice. Similarly, thymic weight variances were smallest for BALB/c and F ₁ mice and highest for C57BL/6 mice. In other studies the body weight responses were examined and gross necropsy observations were recorded for pituitaries and testes during a chronic feeding study with dietary concentrations of DES of 5–640 ppb. A total of 576 mice of each genetic population were used. The dose‐response effect on body weight was examined at about 30 wk in males and 60 wk in females. Body weight variances were smallest for BALB/c mice and largest for F ₂ hybrids. The F ₁ hybrid and C57BL/6 mice were intermediate and indistinguishable from each other. When parameters other than variability were examined (e.g., the time‐ or dose‐dependent body weight responses to DES) the similarity of F ₁ and F ₂ hybrids to one or the other parent strain depended on the end point examined, the sex of the animals, and the duration of exposure to DES. Gross necropsy observations confirmed the expectation that BALB/c males would develop testicular lesions and C57BL/6 mice would develop pituitary lesions in response to DES, while F ₁ and F ₂ hybrid mice developed a relatively high incidence of both types of lesions.