Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine.
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.
Castro
David J
DJ
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.
Yu
Zhen
Z
Löhr
Christiane V
CV
Pereira
Clifford B
CB
Giovanini
Jack N
JN
Fischer
Kay A
KA
Orner
Gayle A
GA
Dashwood
Roderick H
RH
Williams
David E
DE
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001580:Benzopyrenes / Q000633:toxicity*; D002110:Caffeine / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D002392:Catechin / Q000031:analogs & derivatives / Q000627:therapeutic use; D018890:Chemoprevention / Q000379:methods*; D005260:Female; D008431:Maternal-Fetal Exchange; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced* / Q000517:prevention & control*; D010920:Placenta / Q000187:drug effects / Q000473:pathology*; D010936:Plant Extracts / Q000627:therapeutic use*; D011247:Pregnancy; D013662:Tea
D016588:Anticarcinogenic Agents; D001580:Benzopyrenes; D002273:Carcinogens; D010936:Plant Extracts; D013662:Tea; D002110:Caffeine; D002392:Catechin; C045651:epigallocatechin gallate; C041517:dibenzo(a,l)pyrene