1,2-Dimethylhydrazine (
DMH) is a toxic
environmental pollutant which was reported also to be a colon-specific
carcinogen. This study was performed to study the effect of
bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a
bisdemethoxycurcumin analog (
BDMC-A) on
DMH-induced colon
carcinogenesis in male Wistar rats and effects were compared with that of the reference
drug,
curcumin. Rats were given a weekly
subcutaneous injection of
DMH (20mg/kg
body weight) in the groin, for 15 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization)
tumor incidence was 100% in
DMH-treated rats.
Tumor was identified histologically as
adenocarcinoma. Dysplasia, papillary pattern, cellular pleomorphism and carcinomatous glands were also noticed in
DMH-treated rats. However, there was no colonic
tumor in DMH+BDMC-A- and DMH+curcumin-treated rats but, lymphocyte infiltrations were observed. The levels of total
bile acids and
cholesterol in 24h fecal samples were significantly lower in
DMH administered rats when compared to control rats, while, the excretion of
bile acids and
cholesterol were significantly increased and was near normal levels in DMH+BDMC-A- and DMH+curcumin-treated rats. In
DMH-induced
tumor bearing rats the levels of colonic and intestinal
cholesterol was significantly increased whereas, the levels of
phospholipid was decreased with a concomitant increase in the activities of
phospholipase A (PLA) and
phospholipase C (PLC), compared to untreated control rats. Intragastric administration of
BDMC-A and
curcumin to
DMH administered rats significantly lowered the
cholesterol content and raised the
phospholipid content and lowered the activities of PLA and PLC towards near normal values. Our study shows that the protective effect of
BDMC-A during
DMH-induced colon
carcinogenesis may be due to its modulatory effects on (i). histological changes, (ii).
bile acids, (iii).
cholesterol, and (iv).
phospholipid metabolism in the target organ. Absence of histological changes in the colon of rats treated with
BDMC-A, shows that long term administration of
BDMC-A is nontoxic to experimental animals. Our study suggest that
BDMC-A may emerge as a potent anticarcinogenic agent against
colon cancer. As both
BDMC-A and
curcumin are equipotent in inhibiting the
DMH-induced colon
tumor incidence and normalizing histological changes, it could be concluded that the terminal phenolic group and the conjugated double bonds in the central seven
carbon change may be responsible for the beneficial effects.