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Citation
Tags
HERO ID
194627
Reference Type
Journal Article
Subtype
Review
Title
Role of proto-oncogene activation in carcinogenesis
Author(s)
Anderson, MW; Reynolds, SH; You, M; Maronpot, RM
Year
1992
Is Peer Reviewed?
Yes
Journal
Environmental Health Perspectives
ISSN:
0091-6765
EISSN:
1552-9924
Volume
98
Page Numbers
13-24
Language
English
PMID
1486840
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519627/
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Abstract
The accumulation of genetic damage in the forms of activated proto-oncogenes and inactivated tumor-suppressor genes is the driving force in the evolution of a normal cell to a malignant cell. For example, both the activation of ras oncogenes and the inactivation of several suppressor genes, including p53, have been observed in the development of human colon and lung tumors. Point mutations in key codons can activate ras proto-oncogenes and inactivate the p53 suppressor gene. Thus, several critical genes for tumorigenesis are potential targets for carcinogens and radiation that can induce point mutations at low doses. The ras proto-oncogenes are targets for many genotoxic carcinogens. Activation of the ras gene is an early event--probably the "initiating" step--in the development of many chemical-induced rodent tumors. ras Oncogenes are observed in more human tumors and at a higher frequency than any other oncogene, and activation of the proto-oncogene may occur at various stages of the carcinogenic process. Numerous proto-oncogenes other than the ras genes have been shown to be activated in human tumors and to a lesser extent in rodent tumors. Mechanisms that induce aberrant expression of proto-oncogenes are gene amplification and chromosomal translocation or gene rearrangement. Amplification of proto-oncogenes and possibly gene overexpression during the absence of gene amplification occur in the development of many human tumors. For a specific tumor type, amplification of any one proto-oncogene may occur at a low frequency, but the frequency of tumors in which at least one proto-oncogene is amplified can be much higher. Proto-oncogene amplification is usually associated with late stages of tumor progression; however, amplified HER2/neu has been observed in early clinical stages of mammary neoplasia. Activation of proto-oncogenes by chromosomal translocation has been detected at a high frequency in several hematopoietic tumors. Non-ras genes have been detected by DNA transfection assays in both human and rodent tumors. For example, ret and trk genes were found to be activated by gene rearrangements in human papillary thyroid carcinomas. Several potentially new types of oncogenes have also been detected by DNA transfection assays. The etiology of the genetic alterations observed in most human tumors is unclear at present. Examples of ras gene activation and those documented for mutations in the p53 gene demonstrate that exogenous conditions can induce oncogenic mutants of normal genes. The genetic alterations observed in most human tumors are probably generated by both spontaneous events and exogenous conditions.
Tags
IRIS
•
Vanadium Compounds - Problem Formulation
Manual review of existing IRIS and PPRTV assessments
IRIS 2011/2014
Combined data set
Dataset for title/abstract screening
Excluded- PECO criteria not met (TIAB)
•
Vanadium Inhalation
Combined Dataset
Dataset for title/abstract screening
Excluded- PECO criteria not met (TIAB)
•
Vanadium Pentoxide (Draft, 2011)
OPPT REs
•
OPPT_Carbon Tetrachloride_C. Engineering
Total – title/abstract screening
Off topic
•
OPPT_Carbon Tetrachloride_D. Exposure
Total – title/abstract screening
Off topic
•
OPPT_Carbon Tetrachloride_E. Fate
Total – title/abstract screening
Off topic
•
OPPT_Carbon Tetrachloride_F. Human Health
Total – title/abstract screening
Off topic
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