Dose-Related Modulatory Effects of Polymeric Black Tea Polyphenols (PBPs) on Initiation and Promotion Events in B(a)P and NNK-Induced Lung Carcinogenesis

Autor:	Manoj B. Mahimkar, Sadhana Kannan, Rajiv Kumar, Rahul Thorat, A. Ingle, Venkatesh Pai, Rasika Hudlikar, Girish B. Maru
Rok vydání:	2019
Předmět:	Male 0301 basic medicine Cancer Research Lung Neoplasms Nitrosamines Carcinogenesis Cytochrome P-450 CYP1A2 Inhibitors Medicine (miscellaneous) Alpha (ethology) Pharmacology medicine.disease_cause Camellia sinensis DNA Adducts Mice 03 medical and health sciences 0302 clinical medicine Benzo(a)pyrene Cytochrome P-450 CYP1A1 polycyclic compounds medicine Animals Anticarcinogenic Agents Lung Carcinogen Glutathione Transferase 030109 nutrition & dietetics Nutrition and Dietetics Dose-Response Relationship Drug Tea Plant Extracts Chemistry Cell growth CYP1A2 Polyphenols food and beverages Dose–response relationship Liver Oncology Apoptosis 030220 oncology & carcinogenesis Toxicity
Zdroj:	Nutrition and Cancer. 71:508-523
ISSN:	1532-7914 0163-5581
DOI:	10.1080/01635581.2019.1578389
Popis:	Our understanding of dose-related effects of polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, is limited. In the present study, the effect of various doses of black tea (0.75, 1.5, and 3%)-derived PBP-rich extract on biochemical parameters and lung carcinogenicity in A/J mice was investigated. Pretreatment with PBPs showed the dose-related decrease in B(a)P-induced expression and activity of CYP1A1 in the liver while CYP1A2 expression and activity in the lung. Dose-dependent significant increase in PBP-mediated over-expression and activity of GSTs (alpha in the liver while pi in the lung) were observed in polyphenol-treated groups. Significant dose-related decrease in number and intensity of BPDE-DNA adducts were observed in liver and lung. Black tea (1.5%, 3%)-derived PBPs showed dose-mediated decrease in lung tumor incidence and multiplicity which was further correlated with different molecular markers like cell proliferation and apoptosis in B(a)P and NNK model. In conclusion, dose-dependent chemopreventive effects of PBPs, both anti-initiating (induction of phase II and inhibition of carcinogen-induced phase-I enzymes leading to decrease in BPDE-DNA adducts) and anti-promoting (decreased cell proliferation and increased apoptosis lowering incidence and/or multiplicity of lung lesions), were observed in A/J mice without significant toxicity.
Databáze:	OpenAIRE
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