Animal oncogenic viruses

Many animal viruses, particularly the oncogenic viruses—either directly or, in the case of RNA viruses such as HIV that causes AIDS, their DNA transcripts generated by the action of the viral RNA-dependent... 

Recent work has centered upon use of interferon as a therapeutic agent in humans and animals. In humans, local application of monkey interferon is effective in reducing the seventy of vaccinia virus skin infections. Recent results with herpes keratitis and chronic hepatitis are promising. Interferon appears to be active against oncogenic viruses in the treatment of such cancers as osteogenic sarcoma, and at present it is only the limited availability of interferon that pie vents more extensive testing. 

Although ran co-polymer suppressed both ordinary and oncogenic virus infections in animals it produced a number of serious side effects. In man, at intravenous doses of lS-16 mg/kg per day for 8 days it produced fever concurrently with circulating interferon on days 1-4 but not thereafter, but at all doses above 8 mg/kg (which did not produce detectable interferon) it produced thrombocytopenia and was deposited as particulate material chiefly in the spleen but also in blood cells, liver and bone marrow [128]. However, it has recently beai claims from experience in mice and in over 60 human patients to be less toxic than poly I C [132]. 

Other factors to be considered in the assignment of workers include the evaluation of risk to pregnant and immunosuppressed individuals (7, 9, 181, 270), who may need to be reassigned to work that does not not involve oncogenic viruses. A further consideration in evaluating personnel risk is the individual variation in infective dosages that is normally associated with infectious diseases. For example, the sex of the animal has been shown to have an influence on the frequency of successful transmission of tumors (171, 196, 271, 300, 517). 

The characteristics of the agent comprise the third element in assessment of risk. Oncogenic agents are classified according to risk based upon criteria established from the evaluation of animal data. The assumption is made that the infectious dose for an animal is related to the hypothetical human infectious dose. For purposes of risk assessment the risk criteria for oncogenic viruses are divided into three categories high, moderate, and low. 

Cell transformation. This technique is based on the fact that transformation of mammalian cells by carcinogenic chemicals can be observed in tissue culture. In Section 11.5 we discussed cell transformation resulting from oncogenic virus infection similar effects can be observed as a result of chemical transformation. Instead of the orderly growth normally seen in tissue cultures of mammalian cells, cultures of transformed cells spread in a disordered fashion and tend to pile up on top of each other. If the transformed cells are injected into a test animal of the same species and strain that the cells were originally derived from, a malignant tumor will almost invariably result. 

Rabin, H. 1971. Assay and pathogenesis of oncogenic viruses in nonhuman primates. Lab. Anim. Sci. 21 1032-1049. 

Infection by viruses carrying oncogenes can cause malignant cell growth. Although first recognized as causative agents in avian cancers 90 years ago, for much of the twentieth century there was doubt that any human cancers were initiated in this way. Even now, almost all the information in this area refers to nonhuman animals, which presents a number of problems. First, as was already... 

Some representatives of the retroviruses cause tumors in animals such as mice or chickens. The discovery of oncogenes initiated from the src gene of Rous sarcoma virus, which could be identified as the tumor causing principle of this retrovirus. The src gene codes for the Src tyrosine kinase (see 8.3). The gene sections of retroviruses responsible for tumor formation were designated oncogenes. 

The rDNA-derived products may contain potentially harmful contaminants that are normally not present in their equivalents prepared by chemical methods, and which the purification process must be capable of eliminating, such as the endotoxins expressed in bacterial cells, cellular DNA, and viruses of animal origin. Contamination with nucleic acid from transformed mammalian cells is of particular concern due to the possible presence of potentially oncogenic DNA. 

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