S23:Gas/Rauch/Dampf/Aerosol nicht einatmen(geeignete Bezeichnung(en) vom Hersteller anzugeben). S24/25:Berührung mit den Augen und der Haut vermeiden.
Beschreibung
The CYP1A1 (also called aromatic hydrocarbon hydroxylase) is expressed primarily in extrahepatic tissues, small intestine, placenta, skin,
and lung as well as in the liver in response to the presence of CYP1A1 inducers, such as PAHs (i.e., in cigarette smoke and the
carcinogen 3-methylcholanthrene), α-naphthoflavone (a noncarcinogenic inducer related to dietary flavones), and indole-3-carbinol (found
in Brussel sprouts and related vegetables). The CYP1A1 metabolizes a range of PAHs, including a large number of procarcinogens and
promutagens. Diethylstilbestrol and 2- and 4-hydroxyestradiol (catecholestrogens) are oxidized by CYP1A1 to their quinone analogues,
which normally are reduced to inactive metabolites. In the absence of a detoxifying reduction step, however, the quinones may
accumulate and initiate carcinogenic processes or cell death by covalently damaging DNA or cellular proteins. Interindividual variation in
the inducible expression of CYP1A1 might be related to a genetic difference in aromatic hormone (Ah) receptor expression, which could
explain differences in individual susceptibility to cigarette smoke–induced lung cancer.
Biochem/physiol Actions
Cytochrome P450 is a heterogeneous family of isozymes whose primary function is to oxidize small molecules, both as a function of intermediary metabolism (e.g., fatty acids) and to detoxify exogenous compounds (drugs or toxins). Some isoforms have narrow substrate specificity, while others are promiscuous.
Mechanism of action
The mechanism for the induction of the CYP1A1 gene begins with binding of the inducing agents to a cytosolic
receptor protein, the Ah receptor, which is translocated to the nucleus and binds to the DNA of the CYP1A1 gene, thus enhancing its rate
of transcription. The presence of the Ah receptor in hepatic and intestinal tissues may have implications beyond xenobiotic metabolism
and may play a role in the induction of other genes for the control of cellular growth and differentiation. On the other hand, CYP1A1 may
metabolize procarcinogens to hydroxylated inactive compounds that are not mutagenic. The question of how the bowel protects itself from
ingested compounds known to be activated by CYP1A1 (i.e., PAH) remains unanswered.
