Effects on thyroid hormone metabolism and depletion of lung vitamin a in rats by airborne particulate matter

Abstract

Thyroxine (T4) and vitamin A are important regulators of normal epithelial 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). Polychlorinated biphenyls (PCBs) and related organochlorine compounds deplete vitamin A and thyroxine by interaction with TTR and alteration of their metabolism in hepatic and other organs. In the present report an outdoor airborne particulate matter (APM) extract was tested for both interaction 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 characterize compounds present in APM that interact with TTR. A third aim was to compare the interaction of APM extracts with TTR and thyroxine-binding globulin (TBG), the major carrier protein for thyroxine in humans. Results showed that a single treatment of rats with an outdoor APM extract depleted plasma thyroxine and triiodothyronine levels and increased plasma retinol levels gradually over the time period studied, while liver retinol, lung retinol, and retinyl palmitate levels were depleted 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 fraction of the APM extract accounted for most of the inhibitory activity on T4-TTR binding. Polycyclic aromatic hydrocarbons and nitrated derivatives are not likely to be responsible for the activity of the neutral fraction, because several representatives of these compounds showed no or very little interaction with TTR. Pentachlorophenol, a compound with known inhibitory activity on T4-TTR binding, was detected in the organic acid fraction of both a cigarette smoke sample and an outdoor APM sample. Finally, it was shown that several indoor and outdoor APM extracts only interact with TTR, but not with TBG. As APM has the potency to deplete lung vitamin A in vivo and vitamin A might have a protective effect in the process of lung carcinogenesis, APM might increase the susceptibility for the development of lung cancer.

Pathology of Aural Abscesses in Free-Living Eastern Box Turtles (Terrapene Carolina Carolina)

“…In this regard, thyroid hormone and vitamin A metabolism are linked by a com-mon plasma carrier protein, transthyretin (TTR). Polychlorinated biphenyls and related organochlorine compounds deplete vitamin A and thyroxine by interaction with TTR and by alteration of their metabolism in the liver and other organs (Heussen et al, 1993). However, altered differentiation of vitamin A-sensitive epithelia or thyroid or estrogen hormone-sensitive epithelia has not been examined in these animals.…”

Hazardous air pollutants and asthma.

“…Carcinogenic compounds can cause irritation and inflammation at sites of exposure and are often antigenic (251)(252)(253)(254)(255)(256)(257)(258)(259). Respiratory carcinogens (or suspected carcinogens) include antimony compounds (260)(261)(262)(263), arsenic compounds (263)(264)(265)(266)(267)(268), hexamethylphosphoramide (269,270), 4,4´-methylene-bis(2-chloroaniline) (271,272), bromoform (273,274), methylene chloride (275), 4,4´-methylenedianiline (276,277), nitrobenzene (mice) (278-280), 4-nitrobiphenyl (281), 2-nitropropane (282)(283)(284)(285), N-nitroso-Nmethylurea (286), N-nitrosodimethylamine (287)(288)(289)(290), N-nitrosomorpholine (291-293), pentachlorophenol (mice) (294,295), polycyclic aromatic hydrocarbons (250,254,255), 1,3-propane sultone (296,297), propylene oxide (298-300), 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) (301-305), 2,4-toluene diamine (306,307), viny...…”

Relationships Among Aural Abscesses, Organochlorine Compounds, and Vitamin a in Free-Ranging Eastern Box Turtles (Terrapene Carolina Carolina)

“…It is possible that this mechanism may result in an initial accumulation of vitamin A prior to depletion of stores, offering a potential explanation for the apparent paradoxical result. Increased vitamin A levels due to contaminants have been reported in other species (Heussen et al, 1993). In addition, this may provide an explanation for the significant nonlinear relationship between vitamin A concentration and total OC compounds level, whereby there was an initial increase in vitamin A as the OC compound burden increased, followed by a decline as OC compound levels increased further (Fig.…”

“…However, in studies with redeared sliders (Trachemys scripta), o,p9-DDT was found to have higher estrogenic activity than DDT (Sparling et al, 2000). O,p9-DDT is a metabolite of DDT, and some OC compounds are known require metabolization before they are able to interfere with receptor binding (Heussen et al, 1993). Furthermore, even structurally related compounds may have different degrees of biologic activity (Guillette et al, 1995).…”