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Carcinogenesis Advance Access published online on December 10, 2008
Carcinogenesis, doi:10.1093/carcin/bgn280
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Identifying Efficacious Approaches to Chemoprevention with Chlorophyllin, Purified Chlorophylls and Freeze-dried Spinach in a Mouse Model of Transplacental Carcinogenesis

David J. Castro1,2, Christiane V. Löhr3,4, Kay A. Fischer3, Katrina M. Waters5, Bobbie-Jo M. Webb-Robertson5, Roderick H. Dashwood1,2,4, George S. Bailey1,2,4 and David E. Williams1,2,4

1 Department of Environmental and Molecular Toxicology
2 The Linus Pauling Institute
3 College of Veterinary Medicine
4 Environmental Health Sciences Center, Oregon State University , Corvallis, Oregon
5 Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, Washington

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

The carcinogenic potential of dibenzo[a,l]pyrene (DBP) has been well characterized in numerous animal models. We have previously documented that a single dose of 15 mg/Kg DBP to pregnant mice late in gestation (GD 17) produces an aggressive T-cell lymphoma as well as lung and liver cancer in offspring. The current study examines the chemopreventative properties of chlorophyllin (CHL) and chlorophyll (Chl) in this transplacental carcinogenesis model. Pregnant B6129SF1 females, bred to 129S1/SvIm males, received purified diets incorporated with either 2000 ppm CHL, 2000 ppm Chl, or 10% freeze-dried spinach beginning at gestation day 9. Lymphoma-dependent mortality was not significantly altered by maternal consumption of any of the diet and little effect on lung tumor burden in mice surviving to 10 months of age was observed. However, co-administration of CHL at 380 mg/Kg with DBP by gavage (molar ratio of 10:1, CHL:DBP) provided significant protection against DBP initiated carcinogenesis. Offspring born to dams receiving CHL co-gavaged with DBP exhibited markedly less lymphoma-dependent mortality (p< 0.001). The degree of protection by CHL, compared to controls dosed with DBP in tricaprylin (TCP) as the vehicle, was less marked, but still significant. Co-administration of CHL (TCP as vehicle) also reduced lung tumor multiplicity in mice by approximately 50% and this was observed throughout the study (p< 0.005). This is the first demonstration that CHL can provide potent chemoprotection in a transplacental carcinogenesis model and supports a mechanism involving complex-mediated reduction of carcinogen uptake.

Key Words: Transplacental cancer • PAHs: chlorophyllin • lymphoma • lung cancer

Received September 11, 2008; revised December 3, 2008; accepted December 3, 2008.


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