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

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.

• Authors: Barry M Markaverich, Jan R Crowley, Mary A Alejandro, Kevin Shoulars, Nancy Casajuna, Shaila Mani, Andrea Reyna, John Sharp
• Journal: Environmental health perspectives (Environ Health Perspect) Vol. 113 Issue 12 Pg. 1698-704 (Dec 2005) ISSN: 0091-6765 [Print] United States
• PMID: 16330350 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, toxicity)
• Rats
• Rats, Sprague-Dawley
• Receptors, Estradiol (metabolism)
• Sex Factors
• Sexual Behavior, Animal (drug effects)
• Stearic Acids (metabolism, toxicity)
• Tritium
• Zea mays (chemistry)