Inhalation Exposure To Tertiary Amyl Methyl Ether (TAME) Alters The Activities Of Cytochrome P450 Isozymes In Hepatic And Respiratory Tissues Of Sprague Dawley Rats
Weissert, JL; Schatz, RA
| HERO ID | 1299478 |
|---|---|
| In Press | No |
| Year | 2005 |
| Title | Inhalation Exposure To Tertiary Amyl Methyl Ether (TAME) Alters The Activities Of Cytochrome P450 Isozymes In Hepatic And Respiratory Tissues Of Sprague Dawley Rats |
| Authors | Weissert, JL; Schatz, RA |
| Journal | Toxicological Sciences |
| Volume | 84 |
| Issue | 1-S |
| Abstract | Fuel oxygenates, as mandated by amendments to the Clean Air Act of 1990, are blended with gasoline to help reduce harmful vehicle exhaust emissions. To date, methyl-tert butyl ether (MTBE) is the most common oxygenate employed to produce cleaner burning fuels. TAME, as well as ethyl-tert butyl ether and diisopropyl ether, are less commonly used oxygenates; but with the recent launch of the MTBE phase-out program due to health concerns, the demand for TAME may increase. The full impact of TAME on human health, however, is yet to be determined. The aim of this study was to examine the alterations in CYP450 activities in rat nasal mucosa, lung and liver immediately following, and 24 h after, an acute 6 h inhalation exposure to TAME. CYP450 activity was measured in microsomes using specific enzyme probes. TAME (100ppm, 0 h or 24 h) exposure resulted in inhibition of CYP1A1 (69% and 53%), CYP1A2 (96% and 65%), CYP2A3 (89% and 41%), CYP2B1 (44% and 79%), CYP3A (28% and 21%) and CYP4B1 (36% and 23%) in nasal mucosa. Exposure to 300ppm (0 h or 24 h) inhibited nasal mucosal CYP1A1 (79% and 45%), CYP1A2 (80% and 61%), CYP2A3 (84% and 49%), and CYP2B1 (83% and 70%). CYP4B1 was inhibited 27% at 24 h only. In lung, TAME (100ppm or 300ppm) inhibited CYP2A3 (31% and 88%) and CYP2B1 (36% and 22%) at 0 h with recovery to control levels at 24 h. Lung CYP4B1 activity increased 23% immediately following the 300ppm exposure but was subsequently inhibited by 26% at 24 h post-exposure. Hepatic CYP2B1 activity increased at 0 h (87%) and 24 h (207%) following the 300ppm exposure. CYP1A1 activity increased (44%) 24 h following 300ppm only. TAME (100ppm) inhibited CYP3A (16%) at 0 h whereas inhibition of CYP2A3 (27%) and an increase in CYP2E1 activity (19%) occurred 24 h post-exposure in liver. These alterations in CYP450 activity following TAME exposure may lead to adverse human health outcomes upon co-exposure with other agents, such as other solvents in gasoline, by increasing bioactivation and/or delaying detoxication via this system. |
| Is Certified Translation | No |
| Dupe Override | 1299478 |
| Is Public | Yes |
| Language Text | eng |