Aberrant crypt foci and AgNORs as putative biomarkers to evaluate the chemopreventive efficacy of pronyl-lysine in rat colon carcinogenesis

Abstract

Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of potential chemopreventive agents. Our aim was to study the chemopreventive efficacy of pronyl-lysine, a key antioxidant present in bread crust by evaluating, the total number of aberrant crypt foci (ACF), their distributions, dysplastic ACF, colonic tumor incidence and the expression of cell proliferation biomarker such as the argyrophilic nucleolar organizing region-associated proteins (AgNORs) in 1,2-dimethylhydrazine (DMH) induced colon cancer in rats. Male Wistar rats were randomized into seven groups, group 1 were control rats, group 2 received pronyl-lysine (2 mg/kg body weight p.o. everyday), rats in groups 3-7 were administered DMH (20 mg/kg body weight) in the groin for 15 weeks. In addition, group 4 (pre-initiation), 5 (initiation), 6 (post-initiation), and 7 (entire period) received pronyl-lysine (2 mg/kg body weight p.o) everyday. At the end of 34 weeks, pronyl-lysine supplementation showed markedly reduced tumor incidence, ACF development and also lowered number of AgNORs. Overall, these findings confirm that pronyl-lysine has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats.

Silibinin modulates biotransforming microbial enzymes and prevents 1,2-dimethylhydrazine-induced preneoplastic changes in experimental colon cancer

“…The increased body weight gain on silibinin supplementation to DMHtreated rats correlated with decreased tumour incidence and attenuation of DMH carcinogenicity. The results are consistent with our earlier reports with other chemicals (Manju et al, 2005;Panneerselvam et al, 2008).…”

“…Our research is mainly focused on colon cancer chemoprevention, and so far we have unravelled the chemopreventive efficacy of various food-derived nonnutritive agents against 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis (Manju et al, 2005;Sengottuvelan and Nalini, 2006;Panneerselvam et al, 2008). As the development of cancer depends on the dose of carcinogen, the mode of administration and the latent period, this particular method of using DMH (20 mg/kg body weight subcutaneously once a week for the first 15 weeks) and leaving the animals untreated for the rest of the period (latent period) has been already well standardized in our laboratory.…”