Chemistry Reference
In-Depth Information
differentiation, suppression of proliferation, enhanced apoptosis, and reduced DNA
damage (Le Leu et al., 2005, 2007a; Finocchiaro et al., 2008).
DNA damage and apoptosis have been used as biomarkers of colonic cell health
in animal models (Chang et al., 1997). DNA damage is an early step in cancer initia-
tion. Rats fed high-RS2 diets had less DNA damage in rats fed high-protein diets
(Bird et al., 2000; Toden et al., 2003, 2005, 2006, 2007a). Rats were fed diets con-
taining approximately 15, 25, or 35 percent of cooked beef or chicken, both with or
without 20 percent HACS as a source of RS, for 4 weeks. Red meat induced greater
colonic mucus layer thinning than white meat, but HACS was protective in both
cases. Dietary RS protects against the meat-induced damage and also against loss of
the mucus barrier, probably through increased butyrate production. Dietary RS also
attenuated casein, soy, or whey protein-induced colonocyte DNA damage (Toden et
al., 2007b). But DNA damage remained significantly higher in rats fed 25 percent
soy compared with those fed 15 percent protein, indicating that proteins differ in
their effects on these indices of colon health. Inclusion of 10 percent HACS was
found to be sufficient to reduce colonocyte DNA damage, and to increase SCFA
pools in the colon (Toden et al., 2007c).
In a study by Fässler et al. (2007), batch fermentation of RS-enhanced antig-
enotoxic activity and decreased DNA damage by 9 to 30 percent. This suggests that
RS may offer protection for the colon against diet-induced assaults. Using an apop-
tosis model, Le Leu et al. (2005) have showed that rats fed RS2 from HACS had
reduced incidence of neoplasms in the colon and small intestine. HACS (20 percent
in diet) prevented dietary protein-induced colonocyte genetic damage in rats, pos-
sibly through the SCFA butyrate, a bacterial fermentation product of RS (Bajka et
al., 2008).
Apoptosis is a marker of the body's ability to remove damaged cells. Apoptosis
appears to be a better predictor of carcinogenesis than proliferation in induced car-
cinogenesis models (Le Leu et al., 2002). Enhanced apoptotic ability to remove cells
with DNA damage is associated with a reduced risk of colorectal cancer. Prebiotics
such as RS in the form of HACS (20 to 30 percent wt:wt) and oligosaccharides (5 to
10 percent wt:wt) (Le Leu et al., 2003; Hughes et al., 2001) as well as wheat bran were
shown to stimulate the acute apoptotic response to a genotoxic carcinogen (AARGC)
azoxymethane in the rat colon (Hu et al., 2002; Le Leu et al., 2002). The AARGC may
eliminate DNA damaged cells that might otherwise progress to malignancy. Thus,
AARGC may play a role in regulating mutational load in the colon and may have a
protective effect at the early stages in the onset of cancer. In a study by Jacobasch et
al. (1999), the RS-fed rats showed the improvement of the 2,4,6,-trinitrobenzene sul-
fonic acid (TNBS)-induced colonic inflammation as compared to the RS-free group.
Supplementation with SCFAs, such as butyrate and acetate, may protect against
H
2
O
2
insult by postponing menadione-induced ATP (adenosine tri-phosphate) deple-
tion and delaying onset of cell death. SCFAs decrease vulnerability against a H
2
O
2
insult by stimulating DNA repair and antioxidant defense systems. Butyrate pro-
tection against DNA damage may also be related to the protection against apopto-
sis (Abrahamse et al., 1999). Hass et al. (1997) have demonstrated that the absence
of butyrate after the isolation of the colonic epithelium-induced apoptosis and that
