Assessment of micronucleus frequency in the peripheral blood of female rats in persistent estrus treated with selective estrogen receptor modulators

Environ Mol Mutagen. 2012 Jan;53(1):51-4. doi: 10.1002/em.20676. Epub 2011 Aug 29.

Abstract

The aim of this study was to evaluate micronucleus (MN) frequency in polychromatic erythrocytes (PCE) of female rats in persistent estrus (a model developed to mimic polycystic ovary syndrome) treated with selective estrogen receptor modulators (SERMs, tamoxifen, and raloxifene). Forty female Wistar-Hannover rats were divided into four groups of 10 animals each: Group I (normally cycling rats) and Group II (persistent estrus) both received only vehicle, while Group III (persistent estrus) was treated with tamoxifen (250 μg/animal/day) and Group IV (persistent estrus) was treated with raloxifene (750 μg/animal/day). Tamoxifen and raloxifene were given by oral gavage beginning on postnatal day 90 and continuing for 30 consecutive days. Peripheral blood samples were collected from tails 1 day following the last exposure. Blood smears were made on glass slides and stained with 10% Giemsa solution. ANOVA and a Tukey post-hoc test were used for data analysis. Mean percentages of MN were 1.82 ± 0.13, 5.20 ± 0.24, 3.32 ± 0.13, and 3.04 ± 0.12 in Groups I, II, III, and IV, respectively. The results indicate that tamoxifen and raloxifene similarly reduced the formation of MNPCE of female rats in persistent estrus (P < 0.0001 for Groups III and IV vs. Group II), using the dosages and time periods applied in the present study. The data suggest possibly antimutagenic effects of SERMs under high levels of estrogens. The findings also suggest that this is an interesting animal model for studying the genotoxicity of estrogens.

MeSH terms

  • Animals
  • Estrus / drug effects*
  • Estrus / metabolism*
  • Female
  • Micronuclei, Chromosome-Defective / drug effects*
  • Micronucleus Tests
  • Raloxifene Hydrochloride / pharmacology*
  • Rats
  • Rats, Wistar
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Tamoxifen / pharmacology*

Substances

  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Raloxifene Hydrochloride