Cytochrome P450 enzyme activities in the Australian brushtail possum trichosurus vulpesula: a comparison with the rat, rabbit, sheep and chicken.

A comparative study of cytochrome P450 phase 1 biotransformation enzyme activities of the Australian brushtail possum was conducted. Since its introduction to New Zealand this animal pest has caused considerable agricultural and ecological problems. The objective of this work was to probe for potential biochemical weaknesses that may be exploited for designing a more species-specific method of toxicological control of the possum population in New Zealand. Liver microsomal enzyme content and the kinetics of in vitro biotransformation reactions in the possum were quantified and compared with those of the rabbit, rat, chicken and sheep. Significant (p > 0.05) species variations in the liver cytochrome P450 enzyme content were observed. All mammals, including the possum, had considerably higher cytochrome P450, cytochrome b5 and cytochrome reductase levels than the chicken. The chicken had the highest specific phase 1 biotransformation activity (Vmax) for all except 1 of the 8 xenobiotics tested. Among the mammals studied, P450 (Vmax) values in the possum were similar or higher than in the rabbit, rat or sheep. The Km values varied significantly (p > 0.05) between species. The Km for 7-hydroxylation of coumarin was highest in the rat. In comparison with other species, the possum had a lower Km for aromatic hydroxylation of aniline, N-demethylation of N,N-dimethyl aniline, and N-dimethyl aniline, but a higher Km for 0-demethylation of 7-methoxycoumarin, 7-hydroxylation of coumarin, and 0-deethylation of acetophenetidin. It was concluded that phase 1 biotransformation of xenobiotics in the possum is similar to or more efficient than in the other animals tested.