Carcinogenesis Advance Access published online on July 16, 2008
Carcinogenesis, 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, Oregon State University , Corvallis, Oregon
2 The Linus Pauling Institute, Oregon State University , Corvallis, Oregon
3 College of Veterinary Medicine, Oregon State University , Corvallis, Oregon
4 Environmental Health Sciences Center, Oregon State University , Corvallis, Oregon
5 Department of Statistics, Oregon State University , Corvallis, Oregon
To whom correspondence should be addressed: David E. Williams, Department of Environmental and Molecular Toxicology, Oregon State University, ALS1007, Corvallis, OR 97331-7301. Phone: 541-737-3277; FAX: 541-737-7966; E-mail: 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 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 to controls. Induction of Cyp1b1 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.
Key Words: Transplacental • cancer • green tea • lymphoma • lung cancer
Received August 27, 2007; revised September 28, 2007; accepted October 15, 2007.
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