EFFECTS ON THYROID-HORMONE METABOLISM AND DEPLETION OF LUNG VITAMIN-AIN RATS BY AIRBORNE PARTICULATE MATTER

Thyroxine (T4) and vitamin A are important regulators of normal epithe lial differentiation and proliferation and might act in the promotion phase of carcinogenesis. Thyroid hormone and vitamin A metabolism are linked by a common plasma carrier protein, transthyretin (TTR). Polych lorinated biphenyls (PCBs) and related organochlorine compounds deplet e vitamin A and thyroxine by interaction with TTR and alteration of th eir metabolism in hepatic and other organs. In the present report an o utdoor airborne particulate matter (APM) extract was tested for both i nteraction with thyroid hormone and vitamin A metabolism, in order to address the question of whether APM has the potency to deplete vitamin A and thyroid hormones. Furthermore, studies were performed to charac terize compounds present in APM that interact with TTR. A third aim wa s to compare the interaction of APM extracts with TTR and thyroxine-bi nding globulin (TBG), the major carrier protein for thyroxine in human s. Results showed that a single treatment of rats with an outdoor APM extract depleted plasma thyroxine and triiodothyronine levels and incr eased plasma retinol levels gradually over the time period studied, wh ile liver retinol, lung retinol, and retinyl palmitate levels were dep leted by 30-50%. As outdoor APM was able to inhibit T4-TTR binding in vitro, this suggests that the reduction in thyroxine levels in vivo is caused by the same phenomenon. Experiments showed that the neutral fr action of the APM extract accounted for most of the inhibitory activit y on T4-TTR binding. Polycyclic aromatic hydrocarbons and nitrated der ivatives are not likely to be responsible for the activity of the neut ral fraction, because several representatives of these compounds showe d no or very little interaction with TTR. Pentachlorophenol, a compoun d with known inhibitory activity on T4-TTR binding, was detected in th e organic acid fraction of both a cigarette smoke sample and an outdoo r APM sample. Finally, it was shown that several indoor and outdoor AP M extracts only interact with TTR, but not with TBG. As APM has the po tency to deplete lung vitamin A in vivo and vitamin A might have a pro tective effect in the process of lung carcinogenesis, APM might increa se the susceptibility for the development of lung cancer