TY - JOUR
T1 - Further evidence for chemopreventive potential of β-carotene against experimental carcinogenesis
T2 - Diethylnitrosamine-initiated and phenobarbital-promoted hepatocarcinogenesis is prevented more effectively by β-carotene than by retinoic acid
AU - Bishayee, A.
AU - Sarkar, A.
AU - Chatterjee, M.
N1 - Funding Information:
The authors thank Drs. Helene Z. Hill, Amy Davidow, and Anthony Grygotis of New Jersey Medical School for technical advice and support. Dr. Anupam Bishayee is indebted to the Council of Scientific and Industrial Research, Government of India, for financial assistance [Grant 9/96(262)/95-EMR-I] during the execution of the study. Dr. Alok Sarkar acknowledges the financial support as a postdoctoral fellow from the Indian Council of Medical Research, Government of India. Address reprint requests to Dr. Malay Chatterjee, PO Box 17028, Jadavpur University, Calcutta 700 032, India.
PY - 2000
Y1 - 2000
N2 - The comparative effectiveness of β-carotene (BC) and retinoic acid (RA) was investigated against two-stage rat liver carcinogenesis initiated by a single injection of diethylnitrosamine (DEN, 200 mg/kg ip) followed by promotion with phenobarbital (PB, 0.05%) in a basal diet. BC (500 mg/kg) or RA (200 mg/kg) was administered per os daily throughout the entire experiment, before the initiation, or during the promotional stage. Treatment with BC throughout the experiment or before initiation significantly reduced the incidence (p < 0.01), multiplicity (p < 0.05), and size of visible subcapsular hepatocyte nodules (HNs) and reduced (p < 0.001 or 0.05) nodular volume as a percentage of liver volume. The results with RA were of lesser extent than those observed with BC. There was a considerable depletion of hepatic BC and total vitamin A (retinol + ester) in HNs and nonnodular surrounding parenchyma (NNSP) of rats subjected to the DEN-PB regimen than their control counterparts. Treatment with BC significantly elevated hepatic BC and total vitamin A contents in HNs and NNSP compared with DEN-PB control, and the elevation was proportional to the duration of BC treatment. Long-term BC or RA treatment elicited a substantial decrement in reduced glutathione content and γ-glutamyltranspeptidase activity and an increment in cytochrome P-450 content and glutathione peroxidase and glutathione S-transferase activities in the HNs and NNSP, which were otherwise reversed in rats that received DEN-PB treatment alone. Our results suggest that BC or RA has the potential to inhibit DEN-induced hepatocarcinogenesis through selective modulation of the antioxidant defense system and xenobiotic detoxification in the liver. It is also apparent that the beneficial effect of BC or RA is primarily exerted on the initiation phase and secondarily during the promotional stage of DEN-initiated rat liver carcinogenesis and that BC affords a better chemopreventive response than RA.
AB - The comparative effectiveness of β-carotene (BC) and retinoic acid (RA) was investigated against two-stage rat liver carcinogenesis initiated by a single injection of diethylnitrosamine (DEN, 200 mg/kg ip) followed by promotion with phenobarbital (PB, 0.05%) in a basal diet. BC (500 mg/kg) or RA (200 mg/kg) was administered per os daily throughout the entire experiment, before the initiation, or during the promotional stage. Treatment with BC throughout the experiment or before initiation significantly reduced the incidence (p < 0.01), multiplicity (p < 0.05), and size of visible subcapsular hepatocyte nodules (HNs) and reduced (p < 0.001 or 0.05) nodular volume as a percentage of liver volume. The results with RA were of lesser extent than those observed with BC. There was a considerable depletion of hepatic BC and total vitamin A (retinol + ester) in HNs and nonnodular surrounding parenchyma (NNSP) of rats subjected to the DEN-PB regimen than their control counterparts. Treatment with BC significantly elevated hepatic BC and total vitamin A contents in HNs and NNSP compared with DEN-PB control, and the elevation was proportional to the duration of BC treatment. Long-term BC or RA treatment elicited a substantial decrement in reduced glutathione content and γ-glutamyltranspeptidase activity and an increment in cytochrome P-450 content and glutathione peroxidase and glutathione S-transferase activities in the HNs and NNSP, which were otherwise reversed in rats that received DEN-PB treatment alone. Our results suggest that BC or RA has the potential to inhibit DEN-induced hepatocarcinogenesis through selective modulation of the antioxidant defense system and xenobiotic detoxification in the liver. It is also apparent that the beneficial effect of BC or RA is primarily exerted on the initiation phase and secondarily during the promotional stage of DEN-initiated rat liver carcinogenesis and that BC affords a better chemopreventive response than RA.
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U2 - 10.1207/S15327914NC3701_12
DO - 10.1207/S15327914NC3701_12
M3 - Article
C2 - 10965525
AN - SCOPUS:0033839715
SN - 0163-5581
VL - 37
SP - 89
EP - 98
JO - Nutrition and cancer
JF - Nutrition and cancer
IS - 1
ER -