Test 3: 51-52

Question 1

what are some variables that make a person susceptible to cancers

Answer 1

gender and ethnicity, health status, nutrition, young age and genetics

Question 2

Chemically induced and ___ induced mutations are thought to be causative factor in a large majority of human and animal cancers.

Answer 2

oxidative stress

Question 3

Most cancers are “___” in origin

Answer 3

clonal

Question 4

what does it mean when cancer is clonal in nature

Answer 4

cancer begins with genetic and metabolic changes in one or a few cells. These cells then duplicate/ clone rapidly and lead to malignant cells

Question 5

vogelstein model

Answer 5

how cancer forms:

Mutations in the tumor suppressor genes APC and DCC drive the progression of colon epithelial cancer. K-Ras mutation augments proliferation of cells carrying mutations further increase the chances of accumulating additional mutations. P53 is another important tumor suppressor gene and its mutation culminates in the formation of full blown carcinomas, and metastasizing tumors

Question 6

steps of chemical carcinogenesis

Answer 6

chemical carcinogens get taking into the body and activated by cytochrome P450 to become activated carcinogens (UCs).

they body tries to stop by carcinogen inhibitors but mutations in Class II drug metoblizing enzymes leads to UCs binding to DNA and causing mutations

tumor promoters cause cell division of bad cells into hyperplastic nodules

tries to block with cis Retinols, diallyl sulfide and perillyl alochol but if unsuccesful will become neoplasia (cancer)

Question 7

Cancer is a multi-step process and involves a series of mutational events, changes in metabolic profiles, cell cycle ___, and large scale changes in gene ___pattern.

Answer 7

regulation

expression

Question 8

Simple steps involved in chemically induced cancer:

Answer 8

Tumor initiation (mutations induced by DNA reactive chemicals)

tumor promotion (changes in cell cycle progression rapid cell division and changes in gene expression) leading to the formation of hyperplastic nodules

progression to full blown cancer

metastasis.

Question 9

Most chemical carcinogens are inert and they need to be ___ by the host enzyme system.

Answer 9

activated

Question 10

Chemicals activated by ___ enzyme systems contain reactive groups (chemical radicals), or electron deficient group. A majority of them are detoxified by the class II drug metabolizing systems.

Answer 10

cytochrome P450

Question 11

Binding of activated chemicals to DNA and induction of mutations in the critical genes is regarded as the ___step

Answer 11

initiation

Question 12

Tumor promotion is essentially amplification of cells carrying mutations by agents that induce ___ and ___

Answer 12

cell cycle progression and cell proliferation

Question 13

in ___ stage the tumor is still benign and may grow into nodules. At this stage they can be treated surgically, X-ray irradiation or by chemotherapeutic agents

Answer 13

hyperplastic

Question 14

last step of cancer, tumors are aggressive, resistant to apoptosis, ___into other tissues, and cause tissue or system failure. They can still be treated surgically or by new generation of drugs that target specific molecules or signaling pathways that are either specific or predominate in tumor cells.

Answer 14

metastasize

Question 15

tumor initiators

Answer 15

broadly classified as chemical carcinogens. They are invariably lipophilic and inert until metabolically activated by cytochrome p450 monooxygenases (class I drug metabolizing enzymes). Activated chemicals physically bind to DNA and induce mutations or chromosomal damage

Question 16

tumor initiators are invariably ___ and inert until metabolically activated by ___

Answer 16

lipophilic

cytochrome p450 mono-oxygenases (class I drug metabolizing enzymes).

Question 17

tumor promotors

Answer 17

chemicals, which induce cell proliferation and amplify the mutational damage or help populate the damaged cells. These compounds do not directly bind to or interact with DNA and are not mutagenic. Their action is mostly epigenetic in nature

Question 18

___ are chemicals, which induce cell proliferation and amplify the mutational damage or help populate the damaged cells.

Answer 18

tumor promoters

Question 19

Tumor promoters do not directly bind to or interact with DNA and are not ___ . Their action is mostly ___ in nature

Answer 19

mutagenic

epigenetic

Question 20

tumor inhibitors

Answer 20

A) chemicals which detoxify activated carcinogens by direct binding or by altering the electrophylic property of carcinogens. Examples are GSH and gulcuronic acid and their specific transferases enzymes (class II drug metabolizing enzymes)

Chemicals which cause tumor regression by altering the transcription activity of genes involved in cell cycle regulation and cell proliferation

Question 21

examples of tumor inhibitors are

Answer 21

GSH and gulcuronic acid and their specific transferases enzymes (class II drug metabolizing enzymes)

Question 22

___ are chemicals which detoxify activated carcinogens by direct binding or by altering the electrophylic property of carcinogens.

Answer 22

tumor inhibitors

Question 23

tumor inhibitors cause tumor regression by altering the ___ of genes involved in cell cycle regulation and cell proliferation

Answer 23

transcription activity

Question 24

Cytochrome P450 (___ metabolism) enzymes play direct roles in the metabolic activation of carcinogens:

Answer 24

class I drug

Question 25

Metabolic activation of carcinogens to reactive (electron deficient) forms requires a specific CYP isoenzyme, ___ as an electron donor, and ___ as the source of electrons

Answer 25

cytochrome P450 reductase NADPH

Question 26

In the reaction cycle, CYP gets reduced by the transfer of a pair of electrons from ___ and reduced CYP binds to the substrate and O2 and catalyzes the ___ of substrate.

Answer 26

CYP reductase, oxidation

Question 27

mechanism of tumor initiation by metabolically activated by a fungal product often contaminates food and feed, \_\_\_\_

Answer 27

aflatoxin B1

Question 28

Although majority of chemical carcinogens require activation by the CYP monooxygenase system, please note that an important group of environmental/industrial pollutants belonging to the family of \_\_\_, are not metabolized by any of the known class I or class II enzymes

Answer 28

polychlorinated biphenyls (PCB)

Question 29

\_\_\_ belongs to a large family of polycyclic aromatic hydrocarbons that are found in auto exhaust, industrial combustion, cigarette smoke, byproducts of oil and coal industry.

Answer 29

Benzo(α)pyrene (BaP)

Question 30

BaP are potent tumor \_\_\_

Answer 30

initiators

Question 31

Activation of Bap requires ___ that are abundantly found in the hepatic and lung ER fraction (widely called as microsomes) and ___ that is also present in the microsomal fraction of most tissues

Answer 31

CYP1A1 (or 1B1) CYP reductase

Question 32

The activation of BaP occurs by forming ___ in place of a double bond

Answer 32

epoxides

Question 33

Epoxides only on certain position of BaP are reactive to ___ residues on DNA

Answer 33

purine

Question 34

Often epoxides are converted to ___ by the action of epoxide hyrolase.

Answer 34

diols

Question 35

Since BaP contains many double bonds, it can bind to CYP several times and undergo ___ at different position

Answer 35

epoxidation

Question 36

Only the ___ epoxide of BaP is highly DNA reactive.

Answer 36

9:10 this formation will bind easily to the N-7 of guanine of DNA

Question 37

Most mammalian, avian and aquatic species are sensitive to ___ B1 induced liver damage and hepatic cancer.

Answer 37

aflatoxin

Question 38

The aflatoxin B1 epoxide is detoxified by conjugation to \_\_\_.

Answer 38

GSH

Question 39

where is aflatoxin B1 found

Answer 39

fungal toxin, can be found on contaminated peanuts, grains, beans and animal feeds mold = aspergillus flavis

Question 40

\_\_\_ are agents that induce cell cycle and cell proliferation.

Answer 40

Tumor Promoters

Question 41

some examples of tumor promoters

Answer 41

phenobarbital and other barbiturates, alcohol, asbestos, cigarette smoke, lipopolysaccharide and other cytokines, phorbol myristate acetate, plant alkaloids, some food additives, and others

Question 42

. Proliferation of cells carrying mutations in the critical genes associated with oncogenic transformation results in accumulation of population of cells that have ___ regulatory controls

Answer 42

escaped

Question 43

proliferating mutated cells produce increased ___ because of altered metabolism and accumulate more mutations and become highly ___ even in the absence of any external stimuli.

Answer 43

ROS proliferative

Question 44

tumor promotors act like a ___ on cells that have already acquired one or more carcinogenic mutation, causing them to divide and go through \_\_\_, increasing the likelihood that they will acquire more mutations

Answer 44

growth factor S-Phase

Question 45

\_\_\_ represent a Large Family of Non-biodegradable Industrial Pollutants and Carcinogens

Answer 45

PCBs

Question 46

\_\_\_ are a group of 209 aromatic chemicals formed by the chlorination of biphenyls that were widely used as pesticides, defoliating agents, and in various industrial setting until 1979

Answer 46

Polychlorinated biphenyls PCBs

Question 47

\_\_\_ are highly resistant to heat, fire, acids, and they are also non-biodegradable

Answer 47

PCBs PCB, TCDD, DDT, Arochlor, Phenochlor and various organopesticides including “agent orange”

Question 48

Unlike other families of carcinogenic compounds listed such as benzo(a)pyrene and aflatoxin B1 above, PCBs are not metabolized by the ___ and once ingested, they remain in the body until \_\_\_

Answer 48

CYP enzymes death

Question 49

PCBs are associated with many pathological conditions including \_\_\_, tissue inflammation and cancer.

Answer 49

oxidative stress

Question 50

Due to the high lipid solubility and slow metabolism rate of these chemicals, PCBs accumulate in the \_\_\_tissues of almost all organisms

Answer 50

fat rich

Question 51

PCBs cause:

Answer 51

* Probable human carcinogen (breast, bone, brain and skin **cancer**) * **Endocrine disrupter** (binds to estrogen and thyroid hormone receptor and activates aryl hydrocarbon receptor) * **Reproductive toxicity** (induces oxidative stress and protein kinase C cascade) * Neurotoxicity * Immune system suppression

Question 52

PCBs binds to estrogen and thyroid hormone receptor and activates ___ receptor

Answer 52

aryl hydrocarbon

Question 53

PCBs cause reproductive toxicity by induces oxidative stress and ___ cascade

Answer 53

protein kinase C

Question 54

hyper active P450 1 A1 and hypo active NAT are common gene mutations in what ethnicity?

Answer 54

african americans

Question 55

hyper active P4501A1, inactive GSTM1 and slow active epoxide hydrolase are common gene mutations in what ethnicity?

Answer 55

american whites

Question 56

hyper active P4501A1 and slow glycyronyl transferase are common gene mutations in what ethnicity?

Answer 56

hispanic and asians

Question 57

\_\_\_ are chemicals which detoxify activated carcinogens

Answer 57

carcinogen inhibitors

Question 58

examples of carcinogenic inhibitors

Answer 58

antioxidants butylated hydoxy anisole aromatic isothiocyanates flavones

Question 59

antioxidants such as __ and __ will neutralize electron __ groups

Answer 59

Vitamin C and Vitamin E deficient

Question 60

butylated hydorxy anisole will induce ___ like glutathione S transferase and glucuronide transferase

Answer 60

class II drug metabolizing enzymes

Question 61

\_\_\_ come from cruciferous vegtables

Answer 61

aromatic isothiocyantes

Question 62

isthiocyanates induce __ enzymes.

Answer 62

class II drug metabolizing (phenethyl isothiocyanates is an inhibitor to lung cancer)

Question 63

\_\_\_ found in fruit and vegetables induce class II drug metabolizing enzymes

Answer 63

flavones

Question 64

one gene targeted by perilly alcohol is \_\_\_

Answer 64

IGF BP3 (insulin like growth factor binding protein 3) which is an extercellular secreted protein

Question 65

Many tumor cells over express ___ growth factor. Increased extracellular level of ___ essentially blocks the growth factor inducing apoptosis in tumor cells

Answer 65

IGF1 IGF-BP3

Question 66

Compound MF-tricyclic selectively inhibits \_\_\_, the inducible form of enzyme involved in prostanoid biosynthesis.

Answer 66

cycloxygenase2 (COX2)

Question 67

\_\_\_ is an important early indicator of tumor development.

Answer 67

COX2

Question 68

Compound L353381 is selective estrogen modulator (SEM) that inhibits ___ activity in breast cancer cells without affecting estrogenic activities of bone, brain and cardiovascular system.

Answer 68

estrogen receptor

Question 69

L353381 compound has several advantages over currently used drug Tamoxifen for treatment of breast cancer since it does not induce \_\_\_cancers usually associated with Tamoxifen

Answer 69

ovarian or endometrial

Question 70

Compound LG100268 is a ligand that activates some of the “orphan” retinoic acid receptors called \_\_\_, thus helps activation of several of the genes whose expression is lost or subdued in various cancers of epithelial cell origin (lung, breast, intestinal etc.).

Answer 70

RXR

Question 71

By recruiting or activating \_\_\_, LGF100268 helps restore the transcription of important genes (probably some tumor suppressor genes and genes involved in cell cycle control) by activating an otherwise silent transcription factor.

Answer 71

RXR Most of these cancers typically show the loss (deletion) of an important transcription factor, **RARβ.**

Question 72

\_\_\_ is used to prevent intestinal cancers

Answer 72

MF- tricyclic

Question 73

\_\_\_ and ___ are used to prevent breast cancer

Answer 73

L353381 LG100268

Question 74

\_\_\_: an isoflavole (3,5,4’ trihydroxy-trans-stilbene) from the roots of Japanese Knotweed, used in herbal medicine in eastern part of Asia is a potent “Aryl Hydrocarbon Receptor, Ahr” antagonist.

Answer 74

Resveratrol

Question 75

By inhibiting the activation of \_\_\_, and thus restricting the expression of CYP 1 family genes, **Resveratrol** protects against cigarette and environmental toxins induced lung, intestinal and breast cancer.

Answer 75

Aryl Hydrocarbon Receptor,

Question 76

\_\_\_: A polyisoprenylated benzophenone and its derivative isogarcinol from Garcinia Indica fruit have potent anticancer activities on multiple tissue cancers.

Answer 76

garcinol

Question 77

Recent studies show that **garcinol** are potent inhibitors of ___ and other ___ proteins. The anticancer effects of these compounds are directly related to inhibition of histone modification and chromatin remodeling.

Answer 77

p300 HAT (histone acetyltransferase)

Question 78

how does BaP become carcinogentic

Answer 78

cytochrome P4501A1 and 1B1 out on reactive epoxide groups on BaP epoxide hydrolase breaks them down to less toxic form but this causes more problems and creates 9,10 which binds easily to DNA and causes mutations