CYP1A1 and CYP1B1 are extrahepatic P450 family members involved in the
metabolism of procarcinogens, such as PAHs, heterocyclic amines and halogen-containing organic
compounds. CYP1A1/1B1 also participate in the metabolism of endogenous 17-β-estradiol, producing
estradiol hydroquinones, which are the intermediates of carcinogenic semiquinones and quinones.
CYP1A1 and CYP1B1 proteins share approximately half amino acid sequence identity but
differ in crystal structures. As a result, CYP1A1 and CYP1B1 have different substrate specificity
to chemical procarcinogens. This review will introduce the general molecular biology knowledge
of CYP1A1/1B1 and the metabolic processes of procarcinogens regulated by these two enzymes.
Over the last four decades, a variety of natural products and synthetic compounds which interact
with CYP1A1/1B1 have been identified as effective chemo-preventive agents against chemical carcinogenesis.
These compounds are mainly classified as indirect or direct CYP1A1/1B1 inhibitors
based on their distinct mechanisms. Indirect CYP1A1/1B1 inhibitors generally impede the transcription
and translation of CYP1A1/1B1 genes or interfere with the translocation of aryl hydrocarbon
receptor (AHR) from the cytosolic domain to the nucleus. On the other hand, direct inhibitors
inhibit the catalytic activities of CYP1A1/1B1. Based on the structural features, the indirect inhibitors
can be categorized into the following groups: flavonoids, alkaloids and synthetic aromatics,
whereas the direct inhibitors can be categorized into flavonoids, coumarins, stilbenes, sulfur containing
isothiocyanates and synthetic aromatics. This review will summarize the in vitro and in
vivo activities of these chemo-preventive agents, their working mechanisms, and related SARs.
This will provide a better understanding of the molecular mechanism of CYP1 mediated carcinogenesis
and will also give great implications for the discovery of novel chemo-preventive agents in
the near future.