502 RT Iv The Immune System in Health and Disease VISUALIZING CONCEPTS Initially modified tumor cell (b) Mass of tumor cells (localized benign Tumor cells metastasis to occur carried by the blood or lymph to other sites in the ign tumor. ( c) The tumor cells become progressively more inva- body /Adapted from 1 Amell et al., 1990, Molecular Cell Biology sive, invading the underlying basal lamina. The tumor is now 2d ed, Scientific American Books] are said to have undergone malignant transformation, and physical carcinogens appears to involve multiple steps and at they often exhibit properties in vitro similar to those of can- least two distinct phases: initiation and promotion. Initiation cer cells. For example, they have decreased requirements for involves changes in the genome but does not, in itself, lead to rowth factors and serum, are no longer anchorage-dependent, malignant transformation. After initiation, promoters stimu and grow in a density-independent fashion. Moreover, both late cell division and lead to malignant transformation. cancer cells and transformed cells can be subcultured indefi- The importance of mutagenesis in the induction of cancer nitely, that is, for all practical purposes, they are immortal. is illustrated by diseases such as xeroderma pigmentosum. Because of the similar properties of cancer and transformed This rare disorder is caused by a defect in the gene that en- cells, the process of malignant transformation has been stud- codes a DNA-repair enzyme called UV-specific endonuclease. ied extensively as a model of cancer induction. Individuals with this disease are unable to repair UV-induced Various chemical agents(e.g, DNA-alkylating reagents)and mutations and consequently develop skin cancers. physical agents (e.g, ultraviolet ight and ionizing radiation) A number of DNA and RNa viruses have been shown to that cause mutations have been shown to induce transforma- induce malignant transformation. Two of the best-studied tion. Induction of malignant transformation with chemical or are SV40 and polyoma. In both cases the viral genomes,are said to have undergone malignant transformation, and they often exhibit properties in vitro similar to those of can￾cer cells. For example, they have decreased requirements for growth factors and serum, are no longer anchorage-dependent, and grow in a density-independent fashion. Moreover, both cancer cells and transformed cells can be subcultured indefi￾nitely; that is, for all practical purposes, they are immortal. Because of the similar properties of cancer and transformed cells, the process of malignant transformation has been stud￾ied extensively as a model of cancer induction. Various chemical agents (e.g., DNA-alkylating reagents) and physical agents (e.g., ultraviolet light and ionizing radiation) that cause mutations have been shown to induce transforma￾tion. Induction of malignant transformation with chemical or physical carcinogens appears to involve multiple steps and at least two distinct phases: initiation and promotion. Initiation involves changes in the genome but does not, in itself, lead to malignant transformation. After initiation, promoters stimu￾late cell division and lead to malignant transformation. The importance of mutagenesis in the induction of cancer is illustrated by diseases such as xeroderma pigmentosum. This rare disorder is caused by a defect in the gene that en￾codes a DNA-repair enzyme called UV-specific endonuclease. Individuals with this disease are unable to repair UV-induced mutations and consequently develop skin cancers. A number of DNA and RNA viruses have been shown to induce malignant transformation. Two of the best-studied are SV40 and polyoma. In both cases the viral genomes, 502 PART IV The Immune System in Health and Disease VISUALIZING CONCEPTS (a) (b) (c) (d) Initially modified tumor cell Invasive tumor cells Mass of tumor cells (localized benign tumor) Basal lamina Blood vessel Tumor cells invade blood vessels, allowing metastasis to occur FIGURE 22-1 Tumor growth and metastasis. (a) A single cell develops altered growth properties at a tissue site. (b) The altered cell proliferates, forming a mass of localized tumor cells, or be￾nign tumor. (c) The tumor cells become progressively more inva￾sive, invading the underlying basal lamina. The tumor is now classified as malignant. (d) The malignant tumor metastasizes by generating small clusters of cancer cells that dislodge from the tu￾mor and are carried by the blood or lymph to other sites in the body. [Adapted from J. Darnell et al., 1990, Molecular Cell Biology, 2d ed., Scientific American Books.]