| Autor: |
Gary D. Stoner, James K. Selkirk, S. Tong, A. Nikbakht, B. K. Mansfield |
| Rok vydání: |
1984 |
| Předmět: |
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| Zdroj: |
Mutation, Cancer, and Malformation ISBN: 9781461294634 |
| DOI: |
10.1007/978-1-4613-2399-0_20 |
| Popis: |
Chemical carcinogens occur in a number of unrelated chemical structures and comprise a unique set of toxic compounds since they have the common biological endpoint of cancer induction. Characteristically these chemicals are biochemically inert and require some degree of metabolic activation to form the reactive species of the carcinogen molecule. Currently it appears that all reactive forms are electrophilic reagents which readily bind to cellular nucleophiles such as DNA, RNA, and protein. Data from extensive metabolic studies with polycyclic aromatic hydrocarbons and several other carcinogens indicate a qualitative similarity of metabolites formed in both susceptible and resistant species, tissues, and cells. This suggests that there may be divergent processing of the activated carcinogen and/or its immediate precursor that will dictate the probability of the reactive intermediate reaching a critical target site for malignant transformation. Assay of intracellular and extracellular metabolites of benzo(a)pyrene and its relatively inert isomer, benzo(e)pyrene, in epithelial and fibroblast cells display significant biochemical variation and in both conjugation reactions to water-soluble products and the region of the carcinogen molecule where the drug metabolizing enzymes attack. It is critical to the understanding of the mechanism of action of chemical carcinogens to assemble a complete metabolic pathway followed by the parent carcinogen. This includes interspecies variance in terms of processing the molecule from its activated species through formation of its various hydroxylated intermediates and the specificity of the conjugation reactions. Knowledge of these biochemical schemes in concert with the degree of interaction with cellular macromolecules will allow for assembly of the dynamic processing of the carcinogen in both resistant and susceptible tissues and will help explain the diverse activity of the carcinogens. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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