Anti-androgenic activity of 3-methyl-4-nitrophenol in diesel exhaust particles

• Published in: European journal of pharmacology 2006-08, Vol.543 (1), p.194-199
• Main Authors: Li, ChunMei, Taneda, Shinji, Suzuki, Akira K., Furuta, Chie, Watanabe, Gen, Taya, Kazuyoshi
• Format: Article
• Language: English
• Subjects: 3-methyl-4-nitrophenol; Air Pollutants - toxicity; Androgen Antagonists - toxicity; Animals; Anti-androgenic activity; Biological and medical sciences; Biological Assay; Cresols - toxicity; Diesel exhaust particle; Dose-Response Relationship, Drug; Follicle Stimulating Hormone - blood; Genes, Reporter; Genitalia, Male - drug effects; Hershberger assay; Lac Operon; Luteinizing Hormone - blood; Male; Medical sciences; Orchiectomy; Organ Size - drug effects; Pharmacology. Drug treatments; Promoter Regions, Genetic - drug effects; Radioimmunoassay; Rats; Rats, Wistar; Receptors, Androgen - genetics; Recombinant yeast screen assay; Saccharomyces cerevisiae - metabolism; Testosterone - blood; Vehicle Emissions - toxicity
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.06.010

In our continuing studies on nitrophenol derivatives as vasodilators in diesel exhaust particles, we have reported that nitrophenols in diesel exhaust particles possess not only vasodilatory activity but also estrogenic activity in vitro and in vivo, as well as anti-androgenic activity in vitro. Our efforts here were focused on the in vitro and in vivo anti-androgenic activity of 3-methyl-4-nitrophenol (4-nitro- m-cresol; PNMC), known a degradation product of the insecticide fenitrothion, in diesel exhaust particles. We investigated its anti-androgenic activity using an in vitro recombinant yeast screen and in vivo Hershberger assays. Recombinant yeast screen assay showed that PNMC possesses anti-androgenic activity at low concentrations. Furthermore, castrated 28-day-old immature male rats each implanted with a 5-mm-long silastic tube containing crystalline testosterone and injected with PNMC subcutaneously at doses from as low as 0.01 and 0.1 mg/kg up to 1 mg/kg for 5 consecutive days showed significantly decreased weights of the seminal vesicles, ventral prostate, and glans penis. Plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly increased in the 0.1 mg/kg PNMC treatment group. Our results demonstrate that PNMC in diesel exhaust particles clearly has anti-androgenic activity both in vitro and in vivo and can therefore be considered as an endocrine-disrupting chemical.