B. Mukherjee et al., BIOCHEMICAL BASIS OF SELENOMETHIONINE-MEDIATED INHIBITION DURING 2-ACETYLAMINO-FLUORENE-INDUCED HEPATOCARCINOGENESIS IN THE RAT, European journal of cancer prevention, 5(6), 1996, pp. 455-463
Supplementation of selenium in the form of selenomethionine (8 ppm) in
drinking water daily has been found to be highly effective in reducin
g cancer incidence in male Sprague-Dawley rats fed 2-acetylamino-fluor
ine (2-AAF) (0.05%) in the basal diet daily for 16 weeks, Selenomethio
nine treatment before initiation, during initiation or during the sele
ction/promotion phases of hepatocarcinogenesis has been found to be ef
fective in elevating hepatic microsomal cytochrome b5, cytochrome P-45
0 contents, triphosphopyridine nucleotide-cytochrome c-reductase and c
ytosolic aryl hydrocarbon hydroxylase activities to a statistically si
gnificant level measured either in the hyperplastic nodules or in the
non-nodular surrounding liver parenchyma compared with 2-AAF control r
ats, Moreover, selenomethionine treatment throughout the study also de
creased the cytosolic 1-chloro-2,4-dinitrobenzene conjugated glutathio
ne-S-transferase and microsomal UDP-glucuronyl transferase activities
to a significant level when compared with 2-AAF control rats, Furtherm
ore, direct correlations between hyperplastic nodules and non-nodular
liver areas were observed with the hepatic selenium content and also w
ith the rates and patterns of hepatic drug metabolism, Selenomethionin
e was also found to protect and improve the histopathological indices
without any toxic side effects as revealed from the haematoxylin and e
osin staining. Our results establish the fact that selenium is particu
larly protective in limiting the action of 2-AAF during the initiation
phase of hepatocarcinogenesis.