PARENT SESSION
PT2 - Endocrine Disruption
Tuesday, 19 November 2002
8:00 AM to 6:30 PM
Exhibit Hall

(P557) Antiandrogenic activity of extracts of diesel exhaust particulates.

Kizu, Ryoichi^*,1, Okamura, Kazumasa¹, Toriba, Akira, Klinge, Carolyn², Burnstein, Kerry³, Hayakawa, Kazuichi¹, ¹ Kanazawa University, Kanazawa, Japan² University of Louisville School of Medicine, Louisville, Kentucky, USA³ University of Miami School of Medicine, Miami, Florida, USA

ABSTRACT- The atmosphere in urban area is heavily polluted with suspended particulate matter (SPM), and the greater part of SPM is diesel exhaust particulates (DEP) in Japan and Europe. It has been reported that inhalation of diesel exhaust caused the dysfunction of male reproductive system in rats and mice. It is possible that constituents in DEP are involved in the dysfunction. In this study we collected DEP samples emitted from a heavy-duty diesel-engine truck and evaluated the androgenic or antiandrogenic activities of the DEP extracts (DEPEs) on human prostate carcinoma PC-3/AR cells by luciferase reporter gene assay. In the absence of DHT, all the DEPE samples hardly elevated luciferase activity. In the presence of DHT, DEPE samples depressed the DHT-induced luciferase activity. Since DEPE samples did not show significant cytotoxicities, the suppression of DHT-induced luciferase activity by DEPE samples was found to be the antiandrogenic effect. DEPE samples elevated CYP 1A1 mRNA level. -Naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist, reversed the antagonism of DEPE samples. These results indicate that the antiandrogenic effect of DEPE samples is due in part to the constituents acting as AhR agonists. On the other hands, DEPE samples inhibited the binding of testosterone to AR in the competition receptor binding assay, indicating that AR-binding constituents exist in DEPE samples. The AR-binding constituents would bind to AR antagonistically because DEPE samples did not significant androgenic effect. In conclusions, DEPE samples showed the antiandrogenic effect in PC-3/AR cells. This effect was considered to be due in part to constituents that acted as AhR agonists and in other part to constituents that antagonistically bound to AR.

Key words: antiandrogenic activity, diesel exhaust particulate, aryl hydrocarbon receptor