Distribution of lymphoid nodules, aberrant crypt foci and tumours in the colon of carcinogen-treated rats.

Sprague-Dawley rats were given eight weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH) or of vehicle then were sacrificed at 1, 5 or 24 weeks after the last injection of DMH. The locations of pre-existing aggregates of lymphoid nodules (ALNs), the location and multiplicity (size) of aberrant crypt foci (ACF), and the locations of tumours in the colon were determined. A trimodal distribution of pre-existing ALNs along the length of the colon was significantly correlated with the timodal distribution of DMH-induced adenocarcinomas (ACs). A unimodal peak in ACF of all sizes occurred between the sites of two distal ALNs. Thus, the distribution of ACF at 1 or 5 weeks did not correlate with distribution of AC found at 24 weeks. Of the 2640 ACF observed at 1 or at 5 weeks, none were found in the proximal 25% of the colon where ACs eventually occurred. It was concluded that: (1) ALNs play a promotional role in AC formation; (2) the ACs which form in the proximal quarter of the colon seldom if ever form via an ACF precursor; and (3) the location, the number and the size of ACF observed early after DMH exposure did not correlate with the location or predict the incidence of ACs which eventually formed in the colon.