Carcinogenic agents and their cellular interactions

3. Carcinogenic Agents
and their
Cellular Interactions

5. Steps Involved in Chemical Carcinogenesis
Initiation
DNA damage
Promoter
Promoter
Cancer

8. Direct-Acting Carcinogens?
• require no metabolic conversion
• weak carcinogens
• cancer chemotherapeutic drugs (e.g., alkylating agents)
• second form of cancer, usually acute myeloid leukemia.

10. Indirect-Acting Carcinogens
Tobacco
CYP1A1
Metabolic activation
Benzo-pyrene---ULTIMATE CARCINOGEN!
Cancer

11. • cytochrome P-450-dependent
• genes that encode these enzymes are polymorphic
• So inducibility, thus SUSCEPTIBILITY to cancers VARY

13. Molecular Targets of Chemical Carcinogens
Which is the most commonly mutated gene in human cancers?

17. For the sceptic…..
How do we know that smoking causes mutations and then lung cancer?

19. Promotion of Chemical Carcinogenesis
• Promoters are chemical agents that are not mutagenic,
but which instead stimulate cellular proliferation.

21. Radiation Carcinogenesis

25. Nucleotide excision repair

27. Ionising radiation

31. Microbial Carcinogenesis
Can you name a few?

32. Oncogenic RNA Viruses?

33. HTLV 1
Adult T-cell leukemia/lymphoma (ATLL)

37. Neoplastic expansion of Tregs in ATLL may underlie the susceptibility of
affected patients to opportunistic infections, which are a frequent
cause of death

40. Oncogenic DNA Viruses?
• HPV
• Epstein-Barr virus (EBV)
• Hepatitis B virus (HBV)
• Merkel cell polyoma virus
• Kaposi sarcoma herpesvirus (human herpesvirus 8)

42. high-risk HPVs (e.g., types 16 and 18)
squamous cell carcinomas of :
• the cervix
• anogenital region
• head and neck (particularly tumors arising in the tonsillar mucosa)

43. Episomal form-Benign warts
Indonesian “tree man”

47. Epstein-Barr Virus
• African form of Burkitt lymphoma
• B-cell lymphomas in immunosuppressed individuals
a subset of Hodgkin lymphoma
• Nasopharyngeal and some gastric carcinomas
• Rare forms of T-cell lymphoma and natural killer (NK) cell lymphoma

49. Burkitt lymphoma

54. • In contrast to Burkitt lymphoma, 100% of nasopharyngeal carcinomas
obtained from all parts of the world contain EBV
• Unlike Burkitt lymphoma, LMP-1 is expressed in nasopharyngeal
carcinoma cells and, as in B cells, activates the NF-κB pathway.

55. Hepatitis B and C Viruses
70% to 85% of hepatocellular carcinomas

56. Hepatitis B and C Virus infection
immunologically mediated chronic inflammation
hepatocyte death
regeneration
genomic damage
Cancer

57. Helicobacter pylori
Gastric adenocarcinoma
Gastric lymphoma

58. Helicobacter pylori
Chronic Gastritis
Gastric Atrophy
Intestinal metaplasia
Dysplasia
Gastric Adenocarcinoma

59. Helicobacter pylori
H.Pylori reactive T cells
Polyclonal B cell proliferation
Mutations?
MALToma