Direct examination of the clonality of carcinogen-induced colonic epithelial dysplasia in chimeric mice.

The clonal composition of neoplastic foci was examined in histological sections of the colonic epithelium of azoxymethane (CAS: 25843-45-2)-treated CBA/Ca----C57BL/6J mouse aggregation chimeras, with the use of H-2 antigens as markers of cellular genotype. Each of 55 early neoplastic foci occurring at a mosaic patch boundary was composed of cells of a single genotype. Our results provide direct evidence that these foci arise from single crypts. In contrast, the epithelium of 5 of 17 larger adenomas was of mixed genotype: In 3, one genotype was represented only by a rim of cytologically normal epithelium derived from adjacent crypts, but in the other 2 the epithelium of both genotypes was dysplastic. One of these was probably a "collision" tumor arising from adjacent but independent foci; in the other, the minority component may have been derived from entrapped non-neoplastic crypts.