Identifying efficacious approaches to chemoprevention with chlorophyllin, purified chlorophylls and freeze-dried spinach in a mouse model of transplacental carcinogenesis

• Published in: Carcinogenesis (New York) Vol. 30; no. 2; pp. 315 - 320
• Main Authors: Castro, David J., Löhr, Christiane V., Fischer, Kay A., Waters, Katrina M., Webb-Robertson, Bobbie-Jo M., Dashwood, Roderick H., Bailey, George S., Williams, David E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2009; Oxford Publishing Limited (England)
• Subjects: ANIMALS; Anticarcinogenic Agents - therapeutic use; Benzopyrenes; Biological and medical sciences; Cancer Prevention; CARCINOGENESIS; Carcinogenesis, carcinogens and anticarcinogens; CARCINOGENS; Chemical agents; CHLOROPHYLL; Chlorophyll - therapeutic use; Chlorophyllides - therapeutic use; DAMS; DIET; Female; FEMALES; Freeze Drying; HYDRO ENERGY; LIVER; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - prevention & control; Lung Neoplasms - chemically induced; LUNGS; Lymphoma, T-Cell - chemically induced; Lymphoma, T-Cell - prevention & control; LYMPHOMAS; Male; MALES; Maternal Exposure; Maternal-Fetal Exchange; Medical sciences; MICE; MORTALITY; MULTIPLICITY; NEOPLASMS; Plant Preparations - therapeutic use; Pregnancy; PROGENY; SPINACH; Spinacia oleracea; Tumors; Chlorophyll; Animal model; Chemoprophylaxis; Fetal membrane; Placental transfer; Rodentia; Carcinogenesis; Prevention; Vertebrata; Chemotherapy; Mammalia; Treatment; Placenta; Mouse; Spinach; Freeze
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgn280

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 p.p.m. CHL, 2000 p.p.m. 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, coadministration 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 with controls dosed with DBP in tricaprylin (TCP) as the vehicle, was less marked, but still significant. Coadministration of CHL (TCP as vehicle) also reduced lung tumor multiplicity in mice by ∼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 support a mechanism involving complex-mediated reduction of carcinogen uptake.