Dw. Rosenberg et Y. Liu, INDUCTION OF ABERRANT CRYPTS IN MURINE COLON WITH VARYING SENSITIVITYTO COLON CARCINOGENESIS, Cancer letters, 92(2), 1995, pp. 209-214
Repetitive treatment with the organotropic colon carcinogen, 1,2-dimet
hylhydrazine (DMH), produces tumors in susceptible mouse strains that
exhibit pathological features associated with the human disease. As in
human populations, the genetic background of laboratory animals compr
ises a significant component to this organ-specific carcinogenesis, an
d several mouse lines, including AKR/J and DBA/2J are highly resistant
to the tumorigenic effects of DMH. During the course of ongoing studi
es to establish phenotypic differences between susceptible (SWR/J and
P/J) and resistant strains, we have examined the colonic mucosa of DMH
-treated mice for the presence of aberrant crypt foci (ACF). ACF repre
sent an early morphological lesion in stepwise progression of colon ca
ncer. In Experiment 1. 6-week-old SWR/J and AKR/J mice were injected w
ith DMH (35 and 20 mg/kg, respectively) once a week for 2 weeks. Five
weeks later, colons were removed and ACF visualized at low magnificati
on by light microscopy after methylene blue-staining. Only SWR/J mice
revealed focal atypia indicative of preneoplastic change. To obtain ad
ditional information about their morphology, tissue sections containin
g ACF were sectioned and stained with H&E. ACF are larger and have a t
hicker epithelial lining than normal crypts. H&E confirmed the absence
of these lesions in untreated SWR/J and DMH-exposed AKR/J mice. In Ex
periment 2, SWR/J and DBA/2J mice were injected with DMH (35 mg/kg) on
ce a week for 2 weeks. Nine weeks later colons were analyzed for ACF f
ormation. Comparable to the first experiment. no ACF were observed in
the colonic mucosa of the resistant DBA/2J line. In contrast, ACF were
readily identified in the middle and distal colons of similarly expos
ed SWR/J mice. This differential response between resistant and suppor
ts an important role for ACF in the stepwise progression of colon canc
er.