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level: Level 3

Questions and Answers List

level questions: Level 3

Question	Answer
1 → Chemicals that can induce cancer → Can be termed as genotoxic or non genotoxic 2 → __ = a physical or chemical agent that can cause or induce neoplasia	1 Chemical Carcinogens 2 Carcinogen
→ It can interact physically with DNA to damage or change its structure → They are active in their parent form as a product of metabolic activation → The ultimate toxicant can be in parent form or is original structure / chemical form or as a product of metabolic activation → Carcinogens or toxicants that causes alteration or damage to out DNAs	Genotoxic Carcinogens
1 Genotoxic carcinogens can be: 2 Classes of Genotoxic Carcinogens	1 a. Direct-acting carcinogens b. Indirect-acting carcinogen 2 a. Polyaromatic hydrocarbons b. Alkylating agent c. Aromatic amines and amides
→ highly reactive electrophile molecules that causes tumor formation at the site of exposure → They have the ability to spread at different sites, organ or vessel of the body	Direct-acting carcinogens (genotoxic carcinogen types)
→ These are procarcinogens (parent compounds) meaning it requires subsequent metabolism to become a carcinogens → They produce their effect at the target tissue at where metabolic activation occurs and not on the site of exposure (unlike to direct-acting carcinogen)	Indirect-acting carcinogen (genotoxic carcinogen types)
→ __ are usually found in charcoal broiled foods → sunog / itim itim in sinugba / ihaw ihaw → It can also be found in cigarette smoke and diesel exhaust (tambutso)	Benzopyrene (Polyaromatic hydrocarbons) (under Classes of Genotoxic Carcinogens)
→ An example of direct-acting DNA carcinogen	Alkylating agent → It has a several types: 1 Alkyl Alkane Sulfonates (methyl- and ethyl sulfonates) 2 Nitrosamines (N-methyl-N-nitrosourea, N-ethyl-N 3 Nitrosourea 4 N-methyl-N-nitro-N-nitrosoguanidine dimethyl- and diethyl nitrosamines (under Classes of Genotoxic Carcinogens)
→ Undergoes hydrolysis, reduction and oxidation in cytochrome p450 mediated reactions → As a result, it will yield a product which is the hydroxylated metabolites that is often associated with adduct formation in proteins and DNA →As a result, it can cause liver and bladder carcinogenicity / cancer	Aromatic amines and amides (under Classes of Genotoxic Carcinogens)
→ These different metals exhibits distinct carcinogenicity in experimental animals or exposed humans → Those people who have cancer because of metal → are the persons that usually works on mining or factory that handles these metals Exposure: Occupational exposure (exposure because of the nature of its work)	Inorganic carcinogens
→ The chemicals that function thru this mechanism will produce sustained cell death caused by high doses of carcinogenic chemicals such as the chloroform and melamine	Nongenotoxic Chemical Carcinogens
(Nongenotoxic Chemical Carcinogens) Receptor mediated:	A. P450 inducers B. Peroxisome Proliferator-Activated Receptor alpha (PPARA) C. Hormonal mode of action D. DNA methylation and Carcinogenesis E. Oxidative Stress and Chemical Carcinogenesis
1 → aka Phenobarbital 2 → capable of increasing the number and volume of peroxisomes in the cytoplasm of cells 3 → They are oxidative organelles → Frequently, they are molecular oxygen that serves as co-substrates in which hydrogen peroxide is then formed	1 P450 inducers 2 Peroxisome Proliferator-Activated Receptor alpha (PPARA) 3 Peroxisome
→ These chemicals produces liver enlargement and hepatocellular carcinoma in rats and mice → These chemicals bind with Peroxisome Proliferator-Activated Receptor alpha (PPARA) → It will function in the lipid metabolism → Afterwards, it acts as a transcription modulator in gene expression → which lead to ligand activation Agent that inhibits PPara	Herbicides, chlorinated solvents, lipid-lowering fibrate drugs
(Nongenotoxic Chemical Carcinogens) (Receptor mediated:) C. Hormonal mode of action	1● Biogenic amines, steroids, and peptide hormones 2 Estrogenic agent-induce tumors in estrogendependent tissue 3 TSH (Thyroid Stimulating Hormone)
1 → trophic hormones interacts directly with the receptor → they can induce cell proliferation at the target organs → which may lead to the development of tumors when the mechanism is distracted or found at increase persistent levels	1 Biogenic amines, steroids, and peptide hormones
(Estrogenic agent-induce tumors in estrogen-dependent tissue) 1 can cause adenocarcinomas of the vagina and cervix in daughters of woman treated with hormone during pregnancy	1 Diethylstilbestrol (DES)
1 → can cause progression of follicular cell hypertrophy, hyperplasia, and neoplasia 2 It can have an excessive development of follicular cell which is responsible of production of thyroid hormone (the thyroxine T4 and triiodothyronine /T3)	1 TSH (Thyroid Stimulating Hormone) (excessive production of T4 and T3) 2 administered TSH
(Nongenotoxic Chemical Carcinogens) (DNA methylation and Carcinogenesis) Chemicals that causes DNA methylation:	→ Phenobarbital, choline deficiency, diethanolamine
are due to reactive oxygen species and antioxidant unbalance which leads to cellular macromolecules damage → More reactive oxygen species than antioxidant	Oxidative Stress and Chemical Carcinogenesis
(Nongenotoxic Chemical Carcinogens) (Oxidative Stress and Chemical Carcinogenesis) Chemicals that causes oxidative stress:	→ Ethanol, TCDD, Lindane, Dieldrin, Acrylonitrile
mutation of this will result to proliferation of cancer cells / can contribute to proliferation of cancer cells / can contribute to the progressive development of the human cancer	mutations of proto-oncogenes and tumor suppressor genes
→ Have the ability to convert normal cells to cancer cells because one of their function is to control cell growth and proliferation → If their function is damaged — it can proliferate normal cells into cancer cells → Accumulated damage to this can result to altered cell proliferation, differentiation and survival of cancer cells	Proto-oncogenes
→ inhibit the cell proliferation or cell survival of cancer cells → If mutation happens, you cannot kill / undergo apoptosis of the cancer cell	Tumor-suppressor genes
Other biological agents that can promote conversion of normal cells into cancer cells (render cancer):	1. RSV virus (Respiratory syncytial virus) 2. Papilloma virus
1 → This virus can progress into a disease called lung cancer 2 → causes the HPV or may lead to cancer of cervix or cancer caused by cervix through sexually transmitted diseases (can be transmitted from one person to another through sexual contact)	1 RSV virus (Respiratory syncytial virus) 2 Papilloma virus (Human Papillomavirus) hpv = (Human Papillomavirus)