Sequential Chromosomal Alterations in Rat Liver Epithelial Cells During Aflatoxin-Induced Neoplastic Transformation In Vitro

Abstract

Chromosomal changes in liver epithelial cells undergoing AFB1* induced transformation were studied in two well-characterized epithelial cell cultures derived from rat liver. Diploid liver cells, which did not possess any in vitro transformation marker or the ability to induce tumors in vivo, were treated with the hepatocarcinogen AFB1 and the karyotypes were analyzed sequentially at regular intervals. Although a high percentage of aneuploid cells was seen after AFB1 treatment, no “stem-line” was formed during the period studied. Marker chromosomes appeared prior to the acquisition of malignant potential in liver cells treated repeatedly with AFB1. Chromosomes #1 and #2, were found to be preferentially involved in the formation of marker chromosomes induced by AFB1. Neither marker chromosomes nor malignant potential were noted for 22 weeks after a single treatment with AFB1, to an asynchronous population of rat liver cells. However, when a semi-synchronous population of liver cells were treated once with AFB1, marker chromosomes were observed, but only in a small percentage of the cells. Although the direct implication of the chromosomal alterations in the initiation stage of the carcinogenic process is unclear, procedures known to favor the selective growth of transformed cells in vitro and in vivo resulted in a specific enrichment of the cells with marker chromosomes, suggesting that such cells may be important at least in the progression of the carcinogenic process.