Viruses and Animal Tumors

As pointed out in the Glimpse of History, viruses were implicated in causing tumors in chickens in the early twentieth century. Retroviruses are the most important tumor viruses in animals, whereas in humans, DNA viruses are the most important.

Tumor Viruses and Cell Transformation

An understanding of the mechanism by which viruses cause tumors in animals was given a big boost when it was observed that tumor viruses could rapidly change the properties of human cells growing in cell culture. These changes are inheritable and are readily observed. Such changed cells are referred to

Table 14.9 Some Properties of Normal Cells and Tumor Cells in Culture

Normal Cells

1. Cells grow as a monolayer (single layer).

2. Cells grow attached to one another and to glass surfaces.

3. Cells multiply for a limited number of generations and then die, even if diluted into fresh medium.

4. Cells do not form tumors when injected into susceptible animals. Tumor (Transformed) Cells

1. Cells grow in an unorganized pattern and in multiple layers.

2. Cells attach to surfaces less firmly.

3. Cells multiply indefinitely.

4. Cells may form tumors when injected into susceptible animals.

as transformed cells. Note that this phenomenon is quite different from what was discussed already for the transformation of bacteria by naked DNA. The properties of normal and transformed cells in culture are compared in table 14.9.

The properties of the transformed cells in culture are similar to those of tumor cells in the body. Transformed cells do not respond to signals that limit their growth. Thus, whereas normal cells grow as a single or monolayer on a glass surface, transformed cells grow in multiple layers. Also, normal cells go through only a limited number of cell divisions and then die. In contrast, transformed cells growing in tissue culture multiply indefinitely. They are immortal. Further, normal cells stick tightly to the surface of the glass culture dish, whereas transformed cells readily detach from the surface, a phenomenon analogous to metastasizing in the body. Also, when transformed cells in culture are injected into animals, most, but not all, cause tumors. ■ bacterial transformation, p. 203

Once it was discovered that most tumor viruses such as the DNA viruses SV40 and polyoma as well as tumor retro-viruses could transform normal cells in culture, experimentation on tumor viruses became much simpler, cheaper, and faster. To be able to assay the tumor-inducing ability of viruses quickly and cheaply simply by mixing the virions with tissue culture cells greatly expedited research. Within a very short time, the viral genes responsible for cell transformation, the oncogenes, were identified.

How Retroviruses Transform Animal Cells

Retroviruses, the most common cause of tumors in animals, transform cells and cause tumors by inserting transforming genes of the virus into the genome of the host cell (see figure 14.14). The transformation requires that the genetic informa-

Table 14.10 Some Oncogenes Associated with Tumors

Oncogene

Virus

Function of Oncogene

src

Rous sarcoma

Tyrosine protein kinase*

fFps

Fujinami sarcoma virus (chickens)

Tyrosine protein kinase

H-ras

Mouse sarcoma virus

Mutant guanosine triphosphate- binding protein

raf

Mouse sarcoma virus

Serine protein kinase

jun

Avian sarcoma virus

Mutant sequence-specific gene activator

skv

Sloan-Kettering virus

Mutant sequence-specific DNA-binding protein

Oncogenes identified in different retroviruses. Each of these oncogenes corresponds to a proto-oncogene in the host.

*An enzyme that adds a phosphate molecule to tyrosine in a regulatory protein thereby modifying the activity of the protein.

Oncogenes identified in different retroviruses. Each of these oncogenes corresponds to a proto-oncogene in the host.

*An enzyme that adds a phosphate molecule to tyrosine in a regulatory protein thereby modifying the activity of the protein.

14.6 Viruses and Human Tumors 359

In summary, tumors develop from alterations in the function of genes that play critical roles in regulating normal cell growth. These alterations can result from mutations in proto-oncogenes of the cell, or by the introduction of oncogenes of a transforming virus. In all cases, normal cell growth is disrupted.

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  • max
    Do normal cells form tumors when injected into susceptible animals?
    7 months ago

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