The first stage of chemical carcinogenesis results directly from administration of the chemical carcinogen. Initiation is an irreversible, rapid process during which chemical produces permanent changes in DNA of target cells. The second stage is promotion, during which tumor formation is stimulated in tissues that have been exposed to the initiating agent. These tissue and culture changes during the long latency period before the appearance of the first autonomous cancer cell l are usually reversible. The stepwise evolution of cancer cells as they become progressively more malignant is called progression.
All chemical carcinogens can form directly or are metabolized to reactive electrophilic forms.
Can attack the many nucleophilic sites in molecules such as proteins and nucleic acids to form covalent addition products. VHL Inactivation of the VHL gene is the most frequent genetic event in kidney cancer. The 213 amino acid coding sequence of the VHL gene is represented in three exons at chromosome 3p25. The biochemical function of pVHL is still unknown. Normally, the VHL protein associates with several other proteins that regulate transcription and control the cell cycle.