1. polycyclic aromatic hydrocarbons found in tobacco tar
2. Aromatic amines- found in the dye and rubber industry
3. Nitrosamines – in food additives – reason why Japan once had an extremely high rate of gastric cancer. With refrigeration and a marked reduction in nitrosamines, the rate of gastric cancer is now similar to that in the USA
4. Steroid hormones- an example being estrogen – Breakdown products of common substances such as soy can produce estrogen like compounds 5. Cyclamates – used as a sweetener can produces bladder cancer in rats 6. Chemical carcinogenesis is a multistep process
1. Procarcinogen – the conversion of a potentially harmful substance into carcinogen
2. Procarcinogens act on DNA leading to irreversible changes called initiation
3. Promotion – the altered cells proliferate leading to clonal expansion
these include Ultraviolet light (UV), X-rays, radioactive isotopes
A. These act by causing damage to the DNA with breakage. This can lead to point mutations and cross-linking producing cells with unlimited growth
B. An example of a radioactive material that produces cancer is the use of radium on watch faces. The workers licked their brushes and many of them developed tumor of the jaw including osteogenic sarcomas
What do natural biologic carcinogens include?
a toxin from aspergilla and chronic infections of the bladder causes by a parasite Schistosoma haematobium
A. In animals, viral carcinogens have been extensively studied – Feline leukemia in cats and leukemia in chickens
B. DNA viruses are directly integrated into the cell genome
C. RNA viruses have an enzyme reverse transcriptase which can use the RNA to produce fragments of DNA which are incorporated into the genome
What are some examples that cause Cancer?
1. Human papilloma viruses – linked to both benign and malignant tumors of the cervix – recently developed vaccine
2. Epstein-Barr Virus (EBV) – human herpes virus that causes a variety of diseases; Infectious mononucleosis, Burkitt's lymphoma and nasopharngeal cancer. Attacks B cells
3. Hepatitis B virus (HBV) – Transmitted by blood products, associated with increased incidence of liver cancer
What is human RNA virus?
Human T-cell lymphoma/leukemia virus 1(HTLV-I) Is an RNA virus that belongs to retro-viruses like HIV and causes a rare type of T-cell leukemia
What are human Oncogenes?
There are genes in normal cells that have the same structure as viral oncogens (v-onc). These genes are named cellular oncogenes (c-onc) and are mutated normal cellular genes called proto-oncogenes. These proto-oncogenes can be transformed into oncogens by four mechanisms. Normally proto-oncogenes encode proteins that function in growth control
Types of Mutation
A. Point mutation – a single base substitution in the DNA chain
B. Gene amplification – the cell acquires an increased number of copies of the proto-oncogene. The more copies the more malignant the tumor
C. Chromosomal rearrangements – Translocations of one fragment of a chromosome to another or a deletion of part of a chromosome
D. Insertion of the viral genome
What are the Tumor suppressor genes
They suppress tumors!
What are Tumor Supressor genes?
Normal cells have genes called tumor suppressor genes. The two best known are the retinoblastoma gene (Rb-1) and the p53. Loss of the gene Rb-1 leads to the tumor called a retinoblastoma. Gene p53 when lost or mutated has been associated with carcinoma of the colon and the breast
Hereditary Cancer is associated with? and what are some examples?
often associated with the loss of a tumor suppressor gene
A. Examples are Neurofibromatosis type I
B. Hereditary polyposis coli
C. Wilm's tumor
What is the immune response to tumors?
A. There are many natural mechanisms to prevent cancer and the spread. NK cells can destroy tumor cells and Antibody-dependent cytotoxicity may play a role. Cells involved in fighting cancer include lymphocytes macrophages and neutrophils.
B. Evidence for the role of the immune system is the increased number of tumors in immunosuppressed patients.
What are clinical manifestations of neoplasm?
A. Tumors are space occupying and crowd out other structures
B. Tumors selectively take nutrients over other tissues
C. Tumors grow faster than normal tissues
D. Tumors can spread and grow into blood vessels
E. Tumors can produce systemic symptoms like cachexia or weakness
F. Tumors are associated with paraneoplastic syndromes which are causes by tumors remaining well differentiated enough to produce biologically active materials
How has cancer epidemiology been useful?
in the identification of factors related to cancerExamples are gastric carcinomas in Japan when the food was preserved by nitrosamines and bladder cancer in dye workers. In spite of some known car carcinogens the causes of most human cancers remains unknown