Colonic cell proliferation, apoptosis and aberrant crypt foci development in rats given 2-amino-3-methylimidazo[4,5-f]quinoline and treated postinitiation with chlorophyllin
Rh. Dashwood et al., Colonic cell proliferation, apoptosis and aberrant crypt foci development in rats given 2-amino-3-methylimidazo[4,5-f]quinoline and treated postinitiation with chlorophyllin, EUR J CAN P, 10(2), 2001, pp. 139-145
Sodium-copper chlorophyllin (CHL) inhibits the formation of 2-amino-3-methy
limidazo[4,5-f]quinoline(IQ)- and 2-amino-1-methyl-6-phenylimidazo[4,5-b] p
yridine (PhIP)-induced colonic aberrant crypt foci (ACF) and tumours in the
F344 rat when it is given simultaneously with either carcinogen. However,
CHL reportedly increased the incidence of dimethylhydrazine (DMH)-induced c
olon tumours in the same species when administered post-initiation. In the
present study, rats were given IQ (130 mg/kg body weight, by oral gavages o
n alternating days) for 2 weeks, starting in experiment week 3, and one wee
k after the final IQ dose rats received CHL treatment until the study was t
erminated at 16 weeks. Compared with animals given carcinogen alone, the me
an number of IQ-induced ACF per colon was reduced significantly by 1% (w/v)
CHL in the drinking water (P < 0.05), whereas 0.1% and 0.01% CHL had no ef
fect. These CHL concentrations increased in a dose-related manner both the
terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) a
nd bromodeoxyuridine (BrdU) labelling indices in the distal colon. However,
the lowest concentration tested, 0.001% CHL, increased the mean number of
IQ-induced ACF per colon (P < 0.05), and increased the BrdU labelling index
without a concomitant change in TUNEL, These studies indicated that 0.001%
CHL promoted IQ-ACF due to deregulation of the homeostatic balance between
cell birth and apoptosis in the colonic mucosa, whereas higher concentrati
ons of CHL had either no effect or protected against IQ-induced ACF by caus
ing dose-related increases in the overall rate of cell turnover in the colo
n. (C) 2001 Lippincott Williams & Wilkins.