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Chemical xenogenization of experimental tumors
Abstract:
Chemical xenogenization occurs when experimental tumors, treated in vivo or in vitro with selected chemicals, become immunogenic, i.e., able to induce a strong rejection response, immunological in nature, in the histocompatible hosts. Unlike modifications induced by haptens, changes in tumor cell immunogenicity associated with chemical xenogenization are heritable as a result of drug interference with the genetic code. Drugs endowed with potent mutagenic activity are known to be powerful xenogenizing agents, and their mechanism of action is traditionally regarded as involving changes in DNA nucleotide sequence. Triazene and nitrosoguanidine derivatives are among the best known examples of this type of compound, and a large body of information has been accumulated over the years regarding the immunogenic properties of the tumor variants obtained following treatment with those xenogenizing agents. The present paper reviews this information, and also discusses the therapeutic implications of xenogenization in experimental systems of tumor immunotherapy. Xenogenization of murine tumors has also been obtained by means of chemicals devoid of mutagenic activity but capable of affecting gene transcriptional activity. The characteristics of this 'new' type of xenogenization are also reviewed and compared to those of triazene xenogenization.
Insights
Chemical xenogenization enhances tumor immunogenicity, making tumors detectable by the immune system. This process, involving genetic code modification, offers potential for experimental tumor immunotherapy strategies.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Chemical xenogenization induces immunogenicity in experimental tumors.
- This process involves heritable changes in tumor cells, distinct from hapten modifications.
- Mutagenic chemicals like triazenes and nitrosoguanidines are known xenogenizing agents, acting via DNA alterations.
Purpose of the Study:
- To review existing information on chemical xenogenization and its mechanisms.
- To discuss the therapeutic implications of xenogenization in experimental tumor immunotherapy.
- To explore a novel form of xenogenization involving chemicals without mutagenic activity but affecting gene transcription.
Main Methods:
- Review of literature on chemical xenogenization agents and their effects.
- Analysis of tumor variants induced by mutagenic and non-mutagenic chemicals.
- Comparison of xenogenization mechanisms, including DNA sequence changes and transcriptional activity modulation.
Main Results:
- Mutagenic chemicals (triazenes, nitrosoguanidines) induce heritable immunogenicity by altering DNA.
- Chemicals lacking mutagenic activity can also cause xenogenization by affecting gene transcription.
- Both types of xenogenization result in immunogenic tumor variants.
Conclusions:
- Chemical xenogenization is a viable strategy to enhance tumor immunogenicity in experimental models.
- Understanding the mechanisms of xenogenization, including DNA changes and transcriptional modulation, is crucial for immunotherapy development.
- Further research into non-mutagenic xenogenizing agents may offer new therapeutic avenues.