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Effects of green tea on carcinogen-induced hepatic CYP1As in C57BL/6 mice
M Yang1, M Yoshikawa, K Arashidani
1Department of Preventive Medicine/Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, 110-799 Seoul, Korea. myang@snu.ac.kr
Abstract:
Green tea (GT) drinking showed chemopreventive effects on various cancers. In addition, inhibition of CYP1A activity by green tea components--polyphenols--has been suggested as a chemoprevention against carcinogens that were bioactivated by CYP1As. Therefore, any changes in hepatic CYP1As may be considered as a biomarker for GT chemoprevention and clarify whether whole GT is chemopreventive for the population who are exposed to CYP1A specifically-bioactivated carcinogens. In this study, we investigated the changes in CYP1A levels by pre- and concurrent GT drinking against a CYP1A-inducing carcinogen, 3-methylcholanthrene (MC), in aryl hydrocarbon receptor responsive C57 BL/6 mice. We found that GT drinking itself induced hepatic CYP1As and enhanced MC-induced ethoxyresorufin-O-demethylase (EROD) activity (P<0.05). However, our studies of CYP1A monoclonal antibody and western blots revealed that the enhanced hepatic EROD activity by GT did not come from CYP1As. Therefore, our results suggest that GT may work to biotransform CYP1A inducing carcinogens into non-carcinogenic metabolites by modulation of other microsomal enzymes rather than CYP1As. In addition, the mechanism of GT chemoprevention may be different from that of GT components, such as polyphenols that reduce CYP1As activity.
Insights
Green tea (GT) drinking may prevent cancer by altering how the body processes carcinogens. Whole GT enhances carcinogen metabolism via pathways other than CYP1As, suggesting a different mechanism than GT polyphenols.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Green tea (GT) consumption is linked to cancer chemoprevention.
- GT components, like polyphenols, may inhibit CYP1A enzymes, which activate certain carcinogens.
- Investigating whole GT's effect on CYP1A-mediated carcinogen metabolism is crucial for understanding population-level chemoprevention.
Purpose of the Study:
- To determine if whole green tea (GT) drinking alters hepatic CYP1A levels and activity in mice exposed to a CYP1A-inducing carcinogen.
- To clarify the role of CYP1A enzymes in the chemopreventive effects of whole GT against carcinogens bioactivated by CYP1As.
Main Methods:
- Mice (C57 BL/6) were treated with green tea (GT) before and during exposure to 3-methylcholanthrene (MC), a CYP1A inducer.
- Hepatic CYP1A levels and ethoxyresorufin-O-demethylase (EROD) activity were measured.
- Monoclonal antibodies and western blot analysis were used to identify specific enzyme contributions.
Main Results:
- Green tea (GT) drinking alone induced hepatic CYP1As and enhanced MC-induced EROD activity.
- Enhanced EROD activity was not attributed to increased CYP1A levels, as shown by antibody and western blot studies.
- These findings indicate GT modulates other microsomal enzymes, not primarily CYP1As, in biotransforming carcinogens.
Conclusions:
- Whole green tea (GT) chemoprevention against CYP1A-bioactivated carcinogens may involve mechanisms distinct from CYP1A inhibition by GT polyphenols.
- GT appears to enhance the biotransformation of carcinogens through pathways independent of CYP1A modulation.
- Further research is needed to elucidate the specific enzymes and pathways involved in GT's chemopreventive effects.
