Leukotoxin diols from ground corncob bedding disrupt estrous cyclicity in rats and stimulate MCF-7 breast cancer cell proliferation

Environ Health Perspect. 2005 Dec;113(12):1698-704. doi: 10.1289/ehp.8231.

Abstract

Previous studies in our laboratory demonstrated that high-performance liquid chromatography (HPLC) analysis of ground corncob bedding extracts characterized two components (peak I and peak II) that disrupted endocrine function in male and female rats and stimulated breast and prostate cancer cell proliferation in vitro and in vivo. The active substances in peak I were identified as an isomeric mixture of 9,12-oxy-10,13-dihydroxyoctadecanoic acid and 10,13-oxy-9,12-dihydroxyoctadecanoic acid, collectively designated tetrahydrofurandiols (THF-diols). Studies presented here describe the purification and identification of the HPLC peak II component as 9,10-dihydroxy-12-octadecenoic acid (leukotoxin diol; LTX-diol), a well-known leukotoxin. A synthetic mixture of LTX-diol and 12,13-dihydroxy-9-octadecenoic acid (iso-leukotoxin diol; i-LTX-diol) isomers was separated by HPLC, and each isomer stimulated (p < 0.001) MCF-7 cell proliferation in an equivalent fashion. The LTX-diol isomers failed to compete for [3H]estradiol binding to the estrogen receptor or nuclear type II sites, even though oral administration of very low doses of these compounds (>> 0.8 mg/kg body weight/day) disrupted estrous cyclicity in female rats. The LTX-diols did not disrupt male sexual behavior, suggesting that sex differences exist in response to these endocrine-disruptive agents.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Binding, Competitive / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Chromatography, High Pressure Liquid
  • Estrous Cycle / drug effects*
  • Female
  • Housing, Animal
  • Humans
  • Male
  • Mitogens / metabolism
  • Mitogens / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Estradiol / metabolism
  • Sex Factors
  • Sexual Behavior, Animal / drug effects*
  • Stearic Acids / metabolism
  • Stearic Acids / toxicity*
  • Tritium
  • Zea mays / chemistry

Substances

  • 9,10-dihydroxy-12-octadecenoic acid
  • Mitogens
  • Receptors, Estradiol
  • Stearic Acids
  • Tritium