| First Author | Casley WL | Year | 1997 |
| Journal | Fundam Appl Toxicol | Volume | 40 |
| Issue | 2 | Pages | 228-37 |
| PubMed ID | 9441719 | Mgi Jnum | J:45838 |
| Mgi Id | MGI:1196178 | Doi | 10.1006/faat.1997.2394 |
| Citation | Casley WL, et al. (1997) Differences in caffeine 3-demethylation activity among inbred mouse strains: a comparison of hepatic Cyp1a2 gene expression between two inbred strains. Fundam Appl Toxicol 40(2):228-37 |
| abstractText | The 3-demethylation of caffeine can be used as an index of cytochrome P450 CYP1A2 activity in vivo. We compared the plasma levels of caffeine and the 3-demethylated metabolite. 1,7-dimethylxanthine, in six common inbred strains (A/J, P/J, BALB/cJ, C3H/HeJ, AKR/J, and SWR/J) and one inbred strain (APN) derived in our laboratory from outbred Swiss-Webster mice on the basis of its relative susceptibility to acetaminophen-induced hepatotoxicity. We found significant variations between a number of the common strains, all of which produced significantly higher caffeine 3-demethylation indices than our APN strain. In three of the six common strains, there was a significant difference between males and females, with the females having consistently lower 1,7-xanthine/caffeine ratios. Hepatic Cyp1a2 expression was compared between APN and C3H/HeJ males. Microsomal methoxyresorufin O-demethylation, acetanilide 4-hydroxylation, and CYP1A2 immunoreactive protein levels were significantly higher in C3H/HeJ relative to APN mice, as were hepatic CYP1A2 mRNA levels. These results indicate the importance of strain and gender to the outcome of pharmacological or toxicological studies involving CYP1A2-mediated metabolism, as well as the suitability of the plasma 1,7-dimethylxanthine/caffeine ratio as a marker of CYP1A2 activity in the mouse. The striking differences observed between the APN and C3H/HeJ mice suggest that these strains may be suitable for a genetic analysis of the regulation of the basal expression of CYP1A2, a key enzyme in procarcinogen activation. |
