This document discusses chemical carcinogenesis and the initiation and promotion stages. Initiation results from exposure to a carcinogenic agent and causes permanent DNA damage (mutations). Promotion alone cannot cause tumors, but can induce tumors in initiated cells by causing proliferation and clonal expansion of initiated cells. The document also discusses various carcinogens like radiation, viruses, and bacteria that can cause cancer through direct DNA damage or indirect mechanisms like chronic inflammation. It also summarizes tumor immunity, how tumors evade the immune system, and some clinical aspects of cancer like paraneoplastic syndromes and cachexia.

1. Neoplasia 4 Fe A. Bartolome, MD, FPASMAP Department of Pathology Our Lady of Fatima University

2. Chemical Carcinogenesis

5. Initiation alone is not sufficient for tumor formation.

7. For the change to be heritable, the damaged DNA template must be replicated

9. Tumors do not result when the promoting agent is applied before, rather than after, the initiating agent.

11. Mutated cells with reduced growth factor requirements

15. Most are weak carcinogens; some are chemotherapeutic drugs (e.g. Alkylating drugs)

18. Polycyclic hydrocarbons

19. present in fossil fuels; animal fats during process of broiling meats; smoked meat and fish

22. Any gene may be the target  commonly mutated are RAS and p53

24. Degree of risk depends on:Type of UV ray Intensity of exposure Quantity of light-absorbing protective coat of melanin

26. UVB radiation is the main cause of sunburn and skin cancer although mounting evidence suggests UVA may also play a role. UVB does not penetrate the skin as deeply as UVA but has more energy and therefore does more damage to the skin.

27. UVB sunlight is directly absorbed by DNA resulting in single strand breaks and the formation of pyrimidinedimers.

32. Intermediate: breast, lungs, salivary glands

36. Microbial Carcinogenesis

37. Microbial Carcinogenesis

40. Does not contain an oncogene

42. Genes encoding IL-2 & its receptor

55. Impair immune competence  allow sustained B-cell proliferation

57. No consistent pattern of integration in liver cells

63. Implicated in gastric adenocarcinoma and gastric lymphomas

65. Penetrates into gastric epithelial cells  initiate signalling cascade that mimics unregulated growth factor stimulation

70. (+) lymphocytic infiltrates around tumors and in LN draining sites of cancer

71. Increased incidence of cancer in immunocompromised individuals

77. Melanomas: high levels of gangliosides GM2, GD2, and GD3

79. Cancer cells entering the bloodstream form complex thromboemboli with platelets and leukocytes, which are thought to facilitate arrest at ectopic sites, assist interactions with the endothelium, and help in evasion of the immune system. Current data suggest that this phenomenon can be explained by interactions between platelet and/or endothelial P-selectin and carcinoma mucins.

81. Typically normal self-antigens  do not induce immune response

87. Activated by IL-2 and IL-5; may be activated by tumors that fail to express MHC class I antigens

98. Hormone production seen in neoplasms arising in endocrine glands  more typical of benign tumor

103. Two processes involved:Osteolysis induced by cancer Production of calcemichumoral substances in extra-osseous neoplasms

107. Weight loss results equally from loss of fat and lean muscle

110. Provides information about potential behavior of tumor

117. Used for more readily palpable lesions in breast, thyroid, and LN

125. Contribute to detection of cancer