Carcinogenesis Advance Access originally published online on July 16, 2008
Carcinogenesis 2008 29(8):1581-1586; doi:10.1093/carcin/bgm237
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Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine
1 Department of Environmental and Molecular Toxicology
2 The Linus Pauling Institute
3 College of Veterinary Medicine
4 Environmental Health Sciences Center
5 Department of Statistics, Oregon State University, Corvallis, OR 97331, USA
* To whom correspondence should be addressed. Tel: 541 737 3277; Fax: 541 737 7966; Email: david.williams{at}oregonstate.edu
Our laboratory recently developed a mouse model of transplacental induction of lymphoma, lung and liver cancer by the polycyclic aromatic hydrocarbon, dibenzo[a,l]pyrene (DBP). Pregnant B6129SF1 females, bred to 129S1/SvIm males, were treated on day 17 of gestation with an oral dose of 15 mg/kg DBP. Beginning on day 0 of gestation, dams were given (ad lib) buffered water, 0.5% green tea, 0.5% decaffeinated green tea, caffeine or epigallocatechin-3-gallate (EGCG) (both at equivalent concentrations found in tea). The concentration of the teas (and corresponding caffeine and EGCG) was increased to 1.0% upon entering the second trimester, 1.5% at onset of the third trimester and continued at 1.5% until pups were weaned at 21 days of age. Offspring were raised with normal drinking water and AIN93G diet. Beginning at 2 months of age, offspring experienced significant mortalities due to an aggressive T-cell lymphoma as seen in our previous studies. Ingestion of caffeinated, but not decaffeinated, green tea provided modest but significant protection (P = 0.03) against mortality. Caffeine provided a more robust (P = 0.006) protection, but EGCG was without effect. Offspring also developed DBP-dependent lung adenomas. All treatments significantly reduced lung tumor multiplicity relative to controls (P < 0.02). EGCG was most effective at decreasing tumor burden (P = 0.005) by on average over 40% compared with controls. Induction of Cytochrome P450 (Cyp)1b1 in maternal liver may reduce bioavailability of DBP to the fetus as a mechanism of chemoprevention. This is the first demonstration that maternal ingestion of green tea, during pregnancy and nursing, provides protection against transplacental carcinogenesis.
Abbreviations: Cyp, Cytochrome P450; DBP, dibenzo[a,l]pyrene; EGCG, epigallocatechin-3-gallate; PAH, polycyclic aromatic hydrocarbon
Received August 27, 2007; revised September 28, 2007; accepted October 15, 2007.
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