Initiation Promotion Conversion Progression Defects in Terminal Differentiation Defects in Growth Control Resistance to Cytotoxicity Defects in Programmed Cell Death DeaclaicEacrwon Selective D Genetic Clonal Genetic Genetic Genet Expansi Change Change Inhition NORMAL CELL INITIATED PRENEOPLASTIC MALIGNANT CLINICAL CANCER CELL LESION TUMOR CANCER METASTASIS RUS e Activation of Proto-Oncogenes Inactivation of Tumor Suppressor Genes o Inactivation of Antimetastasis Genes Cancer Susceptibility Genes
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Normal cel O) Normal cell line CarcinogenIc agent DNA damage (chemicals and cell mutation Initiation Primary tumour radiation, viruses Metastatic subclone Mutated cell Intravasation Activation of oncogenes by Promotion promoter agent Tumour cell embolus Interaction with Platelets lymphocytes Malignant tumour Progression Extravasation Metastatic tumour. And bIogenesIs
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Initiation Irreversible genetic damage a necessary but insufficient prerequisite for tumor Initiation Activation of proto-oncogene inactivation of a tumor suppressor gene, and etc
13 Initiation • Irreversible genetic damage: A necessary, but insufficient prerequisite for tumor initiation • Activation of proto-oncogene, inactivation of a tumor suppressor gene, and etc
Promotion Promotion: Selective expansion of initiated cells, which are at risk of further genetic changes and malignant conversion Promoters are usually nonmutagenic, not carcinogenic alone. often do not need metabolic activation can induce tumor in conjuction with a dose of an initiator that is too low to be carcinogenic alone Chemicals capable of both initiation and promotion are called complete carcinogens: benzola]pyrene and 4 aminobiphenyl
14 Promotion • Promotion: Selective expansion of initiated cells, which are at risk of further genetic changes and malignant conversion • Promoters are usually nonmutagenic, not carcinogenic alone, often do not need metabolic activation, can induce tumor in conjuction with a dose of an initiator that is too low to be carcinogenic alone • Chemicals capable of both initiation and promotion are called complete carcinogens: benzo[a]pyrene and 4- aminobiphenyl
Malignant conversion The transformation of a preneoplastic cell into that expresses the malignant phenotype Further genetic changes Reversible The further genetic changes may result from infidelity of DNA synthesis May be mediated through the activation of proto-oncogene and inactivation of tumor suppressor gene
15 Malignant conversion • The transformation of a preneoplastic cell into that expresses the malignant phenotype • Further genetic changes • Reversible • The further genetic changes may result from infidelity of DNA synthesis • May be mediated through the activation of proto-oncogene and inactivation of tumorsuppressor gene