To be able to clone individual cells, modify cell behavior, or select mutants, biologists often want to maintain cell cultures for many more than 50 doublings. Such prolonged growth is exhibited by cells derived from some tumors. In addition, rare cells in a population of primary cells may undergo spontaneous oncogenic mutations, leading to oncogenic transformation (see Chapter 24). Such cells, said to be oncogenically transformed, or simply transformed, are able to grow indefinitely. A culture of cells with an indefinite life span is considered immortal and is called a cell line.

Primary cultures of normal rodent cells commonly undergo spontaneous transformation into a cell line. After rodent cells are grown in culture for several generations, the culture goes into senescence (Figure 4-1b). During this period, most of the cells stop growing, but often a rapidly dividing transformed cell arises spontaneously and takes over, or overgrows, the culture. A cell line derived from such a transformed variant will grow indefinitely if provided with the necessary nutrients. In contrast to rodent cells, normal human cells rarely undergo spontaneous transformation into a cell line. The HeLa cell line, the first human cell line established, was originally obtained in 1952 from a malignant tumor (carcinoma) of the uterine cervix and is still used extensively today. Many other human cell lines are derived from cancers, and biologists have rendered others immortal by transforming them to express oncogenes.

Regardless of their source, cells in immortal lines often have chromosomes with abnormal DNA sequences. In addition, the number of chromosomes in such cells is usually greater than that in the normal cell from which they arose, and the chromosome number changes as the cells continue to divide in culture. A noteworthy exception, and exciting development, is a recently described human cell line of hematopoietic origin that is haploid for all chromosomes except chromosome 8. Since inactivation of one of the two copies of a gene in a diploid cell generally does not generate a phenotype, a line with a single copy of most genes should be very useful for genetic analysis, making possible the types of genetic screens employed in model organisms (see Chapter 6). Cells with an abnormal number of chromosomes are said to be aneuploid.