Biology Reference
In-Depth Information
In the mouse, FMO1 and FMO5 are expressed as early as gestation days 15 and
17, and equally between genders until puberty. FMO3 is not expressed until 2 weeks
postpartum and is found equally in males and females until 6 weeks postpartum, when
it becomes undetectable in the male. This developmental pattern, as seen in the female
mouse, is similar to that seen in humans of either gender (
Cherrington et al., 1998a
).
Species Differences
Many species differences in the metabolism of xenobiotics can be explained in terms
of differences in the activity of liver microsomal enzymes (
Brodie and Maickel, 1962;
Quinn et al., 1958; Walker, 1994
), although broad similarities often exist across large
systematic groups. For example,
Barron et al. (1993)
observed that the detoxication of
chlorpyrifos in channel catfish was similar to that in other vertebrates in both phase I
and phase II metabolism. An example of a comparative study of a specific pesticide is
that of
Chin et al. (1979b)
on carbaryl. The gender-dependent expression of FMO iso-
forms also varies between species, as outlined below.
Individual and Strain Differences
Strain and individual differences are often discussed conveniently in terms of tolerance
and resistance, both implying reduced susceptibility to a toxicant. The word
tolerance
is used when the observed decrease in susceptibility occurs in an individual organism
as a result of its own previous or continuing exposure to the particular toxicant or to
some other conditioning stimulus, whereas
resistance
refers to a change in a population
brought about by genetic selection.
Differences in basic levels of enzyme activity have been detected not only among
different species, but also among different strains of mice (
Jay, 1955
), rats (
Quinn et al.,
1958
), rabbits (
Cram et al., 1965
), and birds (
Ronis and Walker, 1989; Walker, 1983
).
Comparative aspects of xenobiotic metabolism, particularly as they relate to CYPs,
were reviewed by
Hodgson (1979)
and
Kulkarni et al. (1975)
.
Gender Differences
Metabolism of xenobiotics may vary with the gender of the organism, and in some
cases differences in overall toxicity between males and females of various species are
known (
Bonate, 1991
). In the absence of induction, microsomal enzyme activity is
often higher in the adult male rat than in females or immature males. However, the
stimulatory effect of xenobiotics on microsomal enzymes is usually greater in females
and immature males than in the adult male rat (
Conney and Burns, 1962
). Gender
differences become apparent at puberty and are usually maintained throughout adult
life. The differences in microsomal monooxygenase activity between males and females
have been shown to be under the control of sex hormones, at least in some species.
Sexually dimorphic CYPs appear to arise, in the rat, by programming, or imprinting,
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