Post on 11-Jan-2016
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CHEMICALS AND CANCER
Toxicology
Cancer Cancer is a term used for diseases in which abnormal cells
divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems.
Tumor or tumour is the name for a swelling or lesion formed by an abnormal
growth of cells (termed neoplastic).Tumor is not synonymous with cancer. A tumor can be benign, pre-malignant,
malignant, whereas cancer is by definition malignant.
Neoplasm Neoplasm is an abnormal mass of tissue as a result of
neoplasia.
Benign tumor are not cancerous. They can often be removed, and, in
most cases, they do not come back. Cells in benign tumors do not spread to other parts of the body.
Malignant tumors are cancerous. Cells in these tumors can invade nearby tissues and spread to other parts of the body. The spread of cancer from one part of the body to another is called metastasis.
Oncogenes
An oncogene is mutated form of proto-oncogene. Proto-oncogenes code for proteins that help to
regulate cellular growth and differentiation. Many abnormal cells normally undergo a programmed
form of death (apoptosis). Activated oncogenes can cause those cells to survive and proliferate. Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer.
RAS, WNT, MYC, ERK, TRK. HER2/neu Products of oncogenes (Growth factor, Receptors,
cytoplasmic kinases, Transcription factors, signal transduction)
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. The gene codes for
Inducer of differentiation Cell adhesion molecules Inhibitor of cellular proliferation Transcription factors Inhibitors of angiogenesis BRCA1, APC, p53
p53
Associated with over 50% of human cancer. Coding of enzyme that are imp for DNA
repair, apoptosis and regulation of cell division.
p53 is guardian of genome. Mutated p53 gene can be inherited. The name p53 is in reference to its
apparent molecular mass:(53kDa). The p53 gene can also be damaged in cells
by mutagens (chemicals, radiation, or viruses).
Characteristics of cancer cell
The malignant phenotype refers to
structural, functional and behavioral differences in the cells of malignant neoplasm.
Loss of contact growth inhibition Autonomy of proliferation Avoidance of apoptosis Aberrant differentiation Induction of angiogenesis
Characteristics of cancer cell
Tumor can be grade from 1 to 4 that
corresponds to its degree of malignancy. Microscopic view of malignant cell Large nucleus Prominent nucleoli Irregularities of chromosomes
Production of embryonic proteins (Alpha-fetoprotein and carcinoembryonic antigen).
Dysplasia "malformation", is a term used in pathology to refer to an abnormality of development.
Definitions
Metaplasia: (change in form) is the reversible replacement of one differentiated cell type with another mature differentiated cell type.
Anaplasia: Reversion of cells to an immature or a less differentiated form, as occurs in most malignant tumors.
Hyperplasia is a general term referring to the proliferation of cells within an organ or tissue beyond that which is ordinarily seen.
Benign and Malignant tumors
Benign tumor can be life threatening (size, location) Adrenal gland, Islets of langerhans of the pancreas.
Carcinoma: epithelial tissue Sarcoma: connective tissue Blastoma: embryonic tissue Melanoma: cancer of melanocyte Leukemia: Sarcoma of blood forming tissue
Benign Tumors & Their Tissue of OriginPrefix Tissue Benign Tumor
NameAdeno- Gland AdenomaChondro- Cartilage ChondromaHemangio-
Blood vessels
Hemangioma
Hepato- Liver HepatomaLipo- Fat LipomaMyo- Muscle MyomaOsteo- Bone OsteomaFibro- Fibrous CT FibromaNeuro- Neural tissue Neuroma
Malignant tumors & their tissue of origin
Adenocarcinoma Glandular epithelium
Squamous cell carcinoma
Squamous epithelium
Osteosarcoma Bone
Chondrosarcoma Cartilage
Lymphosarcoma Lymph node
Liposarcoma Adipose tissue
Retinoblastoma Retinal tissue
Neuroblastoma Neural tissue
Nephroblastoma Renal tissue
Occupational carcinogens
Carcinogen Occupation Cancer type
Asbestos Construction Lung
Benzene Leather Leukemia
Benzidine Dye, rubber Bladder
Chromium Metal worker Lung
Arsenic Pesticides Lung,skin,liver
Tumor angiogenesis, Metastasis &Staging
Angiogenic factorsEndostatin- “Inhibits the angiogenesis
process”
MetastasisCommon location of metastasis
(Lung,liver,bone) The TNM (Tumor, Node and Metastasis)
system.It is one way of determining the prognosis of
the patient.
TNM system for Tumor grading
Primary
Tumor (T)
TX Primary tumor can not be evaluated
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1,T2,T3,T4 Size / extent of primary tumor
Regional
lymph Node (N)
NX Regional lymph node can not be evaluated
N0 No regional lymph node involvement
N1,N2,N3 Involvement of regional L.N(No./extent of spread)
Distant
Metastasis (M)
MX Distant metastasis can not be evaluated
M0 No Distant metastasis
M1 Distant metastasis
Carcinogen
Any substance at any dose, administered by any route, that increases tumor incidence. A carcinogen is a substance that is capable of causing cancer in humans or animals.GenotoxicNon-genotoxic
International Agency for research on cancer (IARC) Group A1: Carcinogenic to humans Group 2A: Probably Carcinogenic to humans Group 2B: Possibly Carcinogenic to humans Group 3: Not classifiable as to its Carcinogenicity to
humans Group 4: Probably not Carcinogenic to humans
Carcinogen Naturally-occurring microbial carcinogen (Aflatoxin
B1)
HBV,HPV, Rous sarcoma virus Dioxins and dioxin-like compounds Industrial smoke and tobacco smoke Vinyl chloride– Plastic industry Radiation (x-rays, gamma, infrared, ultraviolet
radiation) Co-carcinogens: are chemicals that do not
necessarily cause cancer on their own, but promote the activity of other carcinogens in causing cancer (sodium arsenite)
Biotransformation: Less toxic----- more toxic
Carcinogen in food Cooking food at high temperatures, e.g.
grilling or barbecuing meats, can lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke (i.e., benzo pyrene).
Acrylamide is generated in fried or overheated carbohydrate foods (such as French fries and potato chips).
Milk protein Casein, found in milk and many prepared foods, is also a carcinogen. However, independent studies report that casein and other milk proteins protect against cancer.
Genotoxic Genotoxic carcinogens are DNA reactive or
DNA reactive metabolites capable of altering the integrity DNA through direct interaction:
Direct acting Carcinogens: Alkylating agents (Methyl chloromethyl ether) Indirect acting Carcinogens: Aflatoxin, polycyclic hydrocarbon
benz[a]pyrene.
Activation of chemical
Transport to Nucleus
Formation of a DNA adduct
Fixing
Mutation
NonGenotoxic They do not cause directly mutation of
DNA. The mechanism of action is poorly
understood. Not all carcinogens are mutagens. Carcinogenesis is often associated with
changes in methylation of DNA. Asbestos-related cancer associated with long latency periods,often decades
NonGenotoxic Diethylstilbestrol: vaginal and uterine
carcinoma Esterogen: breast cancer
Chemical induced carcinogenesis