TY - JOUR
T1 - Modulation of azaserine-induced pancreatic foci by phenolic antioxidants in rats
AU - Roebuck, B. D.
AU - MacMillan, Denise L.
AU - Bush, Donna M.
AU - Kensler, Thomas W.
N1 - Funding Information:
I Rrreived September 7. 1983; acc('pt('d January 27. 19R1. 'SuppOl"lt'd by Public Health Servir« grants CA-26594 Irom the National Canrcr Institute and ES-07064 [rom the National Insritun of Environmenral Health Sciences and by American Cancer Society grant SIC-3. 'Department of Pharmacology and Toxicology. Dartrnouth Medical School, Hanover, N.H. 03756. 4 Department of Environmental Health Scir-nres, School of Hygiene and Public Health. Johns Hopkins University, Baltimore. Md. 21205. 'We ackno"'ledgr the assistanr« of Dr. John L. S('ed for the ;malysis of reduced glutathion('. Kan-n J. Baumgaruu-r for statistical analyses. and Linda V. Conrad for preparation of this manuscript.
PY - 1984/6
Y1 - 1984/6
N2 - Effects of the dietary phenolic antioxidants butylated hydroxyanisole [(BHA) CAS: 25013-16-5; (1, 1-dimethylethyl)-4-methoxyphenol] and butylated hydroxytoluene [(BHT) CAS: 128-37-0; 2, 6-di-tert-butyl-p-cresol] on pancreatic tumorigenesis were examined. Male LEW inbred rats were given injections of 30 mg azaserine [CAS: 115-02-6; diazoacetate (ester) serine] per kg body weight once a week for 3 weeks and maintained on either a control diet or 0.45% BHA- or 0.45% BHT-supplemented control diet throughout the initiation and post-initiation phases of the experiment. At 4 months post initiation, pancreatic tissue sections were quantitatively examined for the number and size of preneoplastic foci. BHT and BHA treatments reduced the number of acidophilic foci per pancreas by 32 and 48%, respectively, but were without effect on focal size. By contrast, basophilic foci were not subject to modulation by these antioxidants. A constellation of enzyme activities involved in carcinogen inactivation and known to be perturbed by antioxidant treatment was examined in liver and pancreas. The hepatic activities of glucose-6-phosphate dehydrogenase, glutathione reductase, and glutathione-S-transferases were markedly elevated while catalase and Superoxide dismutase activities were unchanged. Glutathione peroxidase activity was diminished. In the pancreas, only glutathione peroxidase activity was affected, and it was reduced in both the BHA and BHT treatment groups. Although the pancreas is refractory to the enzyme inductive effects of these antioxidants, morphometric analysis of foci demonstrated chemoprevention by BHA and BHT of azaserine-induced foci. Whether this reduction reflected inhibition of an initiation, postinitiation, or a combination of effects was not known.
AB - Effects of the dietary phenolic antioxidants butylated hydroxyanisole [(BHA) CAS: 25013-16-5; (1, 1-dimethylethyl)-4-methoxyphenol] and butylated hydroxytoluene [(BHT) CAS: 128-37-0; 2, 6-di-tert-butyl-p-cresol] on pancreatic tumorigenesis were examined. Male LEW inbred rats were given injections of 30 mg azaserine [CAS: 115-02-6; diazoacetate (ester) serine] per kg body weight once a week for 3 weeks and maintained on either a control diet or 0.45% BHA- or 0.45% BHT-supplemented control diet throughout the initiation and post-initiation phases of the experiment. At 4 months post initiation, pancreatic tissue sections were quantitatively examined for the number and size of preneoplastic foci. BHT and BHA treatments reduced the number of acidophilic foci per pancreas by 32 and 48%, respectively, but were without effect on focal size. By contrast, basophilic foci were not subject to modulation by these antioxidants. A constellation of enzyme activities involved in carcinogen inactivation and known to be perturbed by antioxidant treatment was examined in liver and pancreas. The hepatic activities of glucose-6-phosphate dehydrogenase, glutathione reductase, and glutathione-S-transferases were markedly elevated while catalase and Superoxide dismutase activities were unchanged. Glutathione peroxidase activity was diminished. In the pancreas, only glutathione peroxidase activity was affected, and it was reduced in both the BHA and BHT treatment groups. Although the pancreas is refractory to the enzyme inductive effects of these antioxidants, morphometric analysis of foci demonstrated chemoprevention by BHA and BHT of azaserine-induced foci. Whether this reduction reflected inhibition of an initiation, postinitiation, or a combination of effects was not known.
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U2 - 10.1093/jnci/72.6.1405
DO - 10.1093/jnci/72.6.1405
M3 - Article
C2 - 6610071
AN - SCOPUS:0021244331
SN - 0027-8874
VL - 72
SP - 1405
EP - 1410
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 6
ER -