Abstract
The cytology of hepatic cells during the process of carcinogenesis was studied in rats fed with a protein-deficient DAB (4 - dimethylaminoazobenzene) diet. Emphasis was placed on the induction of mitotic irregularities and the formation of cells containing aneuploid amounts of DNA, which was quantitatively determined by the microphotometric method of Patau. The results indicate that DAB causes severe damage to the cells, ranging from chromosomal abnormalities such as chromosome fragments and bridges to spindle irregularities such as tripolar mitoses and unequal chromosome distribution. These abnormal mitoses lead to the formation of a population consisting of cells with different aneuploid amounts of DNA. The alteration from a genetically homogeneous to a genetically heterogeneous cell population occurs in the precancerous liver of DAB-fed rats before any definite tumors can be recognized. The hepatomas studied contain cells having a predominantly subtetraploid DNA content or a multiple of this aneuploid DNA value. Two hepatomas of the same liver lobe can differ from each other in their average DNA content. The significance of mitotic abnormalities, the occurrence of a genetically heterogeneous cell population, and the selection of a particular cell line are discussed in regard to the formation of neoplastic cells.