Pathology part 2

• 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

Atomic radiation.

• 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

a toxin from aspergilla and chronic infections of the bladder causes by a parasite Schistosoma haematobium

• 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

• 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

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

• 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

They suppress tumors!

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

often associated with the loss of a tumor suppressor gene

• A. Examples are Neurofibromatosis type I
• B. Hereditary polyposis coli
• C. Wilm's tumor

B. Evidence for the role of the immune system is the increased number of tumors in immunosuppressed patients.

• 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