Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine.

Abstract

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.

• Authors: David J Castro, Zhen Yu, Christiane V Löhr, Clifford B Pereira, Jack N Giovanini, Kay A Fischer, Gayle A Orner, Roderick H Dashwood, David E Williams
• Journal: Carcinogenesis (Carcinogenesis) Vol. 29 Issue 8 Pg. 1581-6 (Aug 2008) ISSN: 1460-2180 [Electronic] England
• PMID: 18635525 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Benzopyrenes
• Carcinogens
• Plant Extracts
• Tea
• Caffeine
• Catechin
• epigallocatechin gallate
• dibenzo(a,l)pyrene

Topics

• Animals
• Anticarcinogenic Agents (therapeutic use)
• Benzopyrenes (toxicity)
• Caffeine (pharmacology)
• Carcinogens (toxicity)
• Catechin (analogs & derivatives, therapeutic use)
• Chemoprevention (methods)
• Female
• Maternal-Fetal Exchange
• Mice
• Neoplasms (chemically induced, prevention & control)
• Placenta (drug effects, pathology)
• Plant Extracts (therapeutic use)
• Pregnancy
• Tea