BCH 475 Biochemistry of Carcinogenesis Professor A. S. Alhomida Summer, 2008 Part 4 Disclaimer The texts, tables and images contained in this course presentation are not my own, they can be found on: – References supplied – Atlases or – The web sites King Saud University College of Science Department of Biochemistry 1
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BCH 475 Biochemistry of Carcinogenesis Professor A. S. Alhomida Summer, 2008 Part 4 BCH 475 Biochemistry of Carcinogenesis Professor A. S. Alhomida Summer,
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BCH 475Biochemistry of Carcinogenesis
Professor A. S. AlhomidaSummer, 2008
Part 4
BCH 475Biochemistry of Carcinogenesis
Professor A. S. AlhomidaSummer, 2008
Part 4
DisclaimerThe texts, tables and images contained in this course presentation are not my own, they can be found on: – References supplied– Atlases or– The web sites
King Saud University
College of Science
Department of Biochemistry
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Eating to Prevent Cancer
How a Healthy Diet and Physical Activity May Help
Keep You Cancer-Free
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The Relationship Between Lifestyle and cancer
A total of 60-70% of cancers may be lifestyle related!
30-40% of cancers can be prevented by a healthy diet, healthy weight, and regular physical activity
30% of cancers can be prevented by not using tobacco
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The Relationship Between Lifestyle and cancer
Many foods and nutrients have been linked to cancer prevention
For cancer prevention, focus on an overall healthy diet rather than specific foods or nutrients
Maintain a healthy weight throughout life
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The Relationship Between Lifestyle and cancer
Adopt a physically active lifestyle
Eat a variety of foods, with an emphasis on plant sources
Limit consumption of alcoholic beverages
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Maintain a Healthy Weight
Being overweight and inactive accounts for 1/3 of the worldwide cases of breast, colon, endometrial, kidney, and espophageal cancers
Balance calorie intake with physical activity
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Maintain a Healthy Weight
Avoid excessive weight gain throughout life
Achieve and maintain a healthy weight if currently overweight or obese
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Body Mass Index (BMI)
Body mass index is defined as the individual's body weight divided by the square of their height
BMI provides a reliable indicator of body fatness for most people and is used to screen for weight categories that may lead to health problems
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Body Mass Index (BMI)
It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing "social physics"
The formulas universally used in medicine produce a unit of measure of kg/m2
Body mass index may be accurately calculated using the formulas below:
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Maintain a Healthy Weight
Body Mass Index (BMI)
)(
)(22 mheight
kgweightBMI
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Maintain a Healthy Weight
Know your Body Mass Index (BMI)Below 18.5 Underweight
18.5 – 24.9 Normal weight25.0 – 29.9 Overweight30.0 and Above Obese
Adults: – Get at least 30 minutes or more moderate to
vigorous physical activity five or more days of the week, 45-60 minutes if possible
Children and adolescents: – Get 60 minutes per day of moderate to
vigorous physical activity at least five days per week
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Healthy Foods
Eat a variety of healthy foods with an emphasis on plant foods
Plant foods (fruits, vegetables, whole grains, and legumes) are packed with vitamins, minerals, antioxidants, and other substances that work together to lower risks of several cancers
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Cancers Associated with Low Intake of Plant Foods
Lung cancer
Mouth cancer
Stomach cancer
Colon cancer
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Healthy Foods
Eat five or more servings of fruits and vegetables each day
Choose whole grains over processed (refined) grains and sugars
Limit consumption of processed red meats
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Healthy Foods
Fruits and vegetables are rich in fiber, vitamins, minerals, and phytochemicals
Whole grains are rich in fiber, vitamins, minerals, and phytochemicals
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Healthy Foods
They contain several substances that have been linked to lower cancer risk including fiber, antioxidants, phenols, lignans, polyestrogens, and saponins
Standard serving sizes: – One cup raw fruit or vegetable, ½ cup canned
fruit or cooked vegetable, one medium piece of fruit, ¼ cup dried fruit
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Fruits and Vegetables
Choose five or more servings of fruits and vegetables each day
Choose colorful fruits and vegetables for the most nutrient content
Choose a variety of fruits and vegetables
Enjoy fruits and vegetables prepared and served without added fat or sugar
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Fruits and Vegetables
One serving equals:– ½ cup cooked vegetables– One cup leafy vegetables– ½ cup 100% juice– One medium piece of fruit– ½ cup fresh, frozen, or canned fruit, or ¼ cup
dried fruit
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Cancers Associated with Alcohol Intake
Oral (mouth)
Pharyngeal (throat)
Esophageal
Laryngeal (voice box)
Breast
Liver– Use of tobacco at the same time as alcohol
increases your risk for developing these cancers
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Dietary Factors Associated with Reduced Cancer Risk
Dietary fiber– Colorectal, pancreas, breast
Folic acid– Cervix, colorectal
Vitamin D and calcium – Colorectal, breast
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Dietary Factors Associated with Reduced Cancer Risk
Vitamin C from foods – Oral cavity, esophagus, lung, stomach,
pancreas, cervix
Tea (flavonoids)Lung, colorectal
α-tocopherolLung
Soy isoflavones?Breast
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Dietary Factors Associated with Reduced Cancer Risk
Antioxidants (nutrient and non-nutrient) from foods– Colorectal, lung, breast, cervix, prostate,
esophagus, stomach
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Food Components that May Prevent Cancer
Antioxidants – Vitamins A, C, E, cartenoids, selenium– There is no evidence to support taking
antioxidant supplements to prevent cancer
Dietary fiber– The link between fiber and cancer is weak– Foods that contain fiber are high in other
nutrients that may prevent cancer
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Food Components that May Prevent Cancer
Phytochemicals– Compounds made by plants that may prevent
cancer (e.g., lycopene in tomato)– There is no evidence that phytochemical
supplements prevent cancer– Lycopene is a phytochemical (red-orange
carotene pigment found in tomatoes and other pink and red fruits and vegetables)
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Food Components that May Prevent Cancer
Phytochemicals– Several studies report that consuming tomato
products reduces the risk of some cancers but the link with lycopene is uncertain
– This has been highly touted as preventing prostate cancer based on one study
– Further studies are in process
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Food Components that May Prevent Cancer
Vitamin D– There is growing evidence that vitamin D may
help prevent colon, prostate, and breast cancer
– In some cases supplements are recommended
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Food Components that May Prevent Cancer
Vitamin D– Research is needed to determine how much
vitamin D is needed by different populations, but it appears to current Dietary Reference Intakes’ (DRI) may be inadequate to prevent cancer
– A balanced diet, moderate supplementation, and frequent sun exposure (small amounts) are preferred method to obtain Vitamin D
Reaction with Cellular TargetsDNA Damage, Mutagenesis
Inhibitors of Activation
Blocking Agents
Suppressing Agents
Exposure to Carcinogen
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Inhibitors of Activation
Inducers of Phase I Biotransformation Enzymes– Cytochrome P450 mono-oxygenase system– Converts hydrophobic to hydrophilic
compounds for elimination by forming reactive intermediate
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Phase I Activation and Phase II Detoxification Reactions
Carcinogen PrimaryMetabolite
SecondaryMetabolite
Reactive Intermediate
Covalent Binding
Acute CellularInjury
DelayedToxicity
Mutations & Cancer
Excretion
Bioactivation Detoxification
Phase I Phase II
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Blocking Agents
Inducers of phase II detoxification Enzymes– Glutathione S-transferases, sulfotransferases,
UDP-gluronosyltransferases– Phenols, isothiocyanates, flavones, and
coumarins– Affect gene expression at transcriptional level
Binders of free radical intermediates– Antioxidants
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Suppressing Agents
Inhibit development of cancer subsequent to administration of carcinogen– Retinoids and carotenoids– Protease inhibitors– Phenols and polyphenols– Selenium
Antioxidant protection
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Role of Antioxidants in Carcinogenesis
Reactive O2
+O2-Derived
Free Radicals
Oxidized basesin DNA
Normal cell
Lipid peroxidationin cell membranes
Cell repairExposure of DNACell DeathLipid Peroxides
DNA Repair
Normal Cell
Mutations Cell DeathNo Repair
CompensatoryCellularHypoproliferation
Less regulation of cellgrowth & differentiation
Cell Hyperproliferation
Exposure of DNA
Further Mutations
Antioxidant Scavengers &
Enzyme Systems
Antioxidant Protection
C ata laseP eroxid ase
G lu ta th ion eP eroxid ase
S u p eroxid eD ism u tase
E n zym e S ys tem sM in era ls
M em b ran eL ip id
P ro tec tion
A q u eou sC om p tm ts
L ip idC om p tm ts
S caven g ersV itam in s
C e llu la rA n tioxid an ts
Non-nutrient Plant Chemicals
Cu/Mn E C CarotenoidsSe, AAFe
PolyphenolsIsothiocyanates
CoQ10
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Other Protective Effects: Folic Acid
Thymidine synthesis inhibited
Lack of methyl donor from methylene-THF
or S-adenosyl-methionine
DNA hypomethylation
Uracil misincorporation
DNA repair by excision
Increase in fragile sites and chromosomal breaks
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Folate Deficiency and DNA Stability
single strandbreak
double strandbreak
DNA TMP dUMP
CH3
X
DNA repair removesmisincorporated
uracil
Chromosomal damage
U A
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Moderators of Insulin Sensitivity and Resistance
Moderators of insulin and insulin-like growth factor (IGF-1)– IGF-1 protects against apoptosis– Insulin and IGF-1 increase aberrant crypt foci
growthPrecursor of colorectal tumors
– Insulin resistance associated with increased tumor promotion in animal models (r = 0.67)
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Insulin Resistance and Relative Risk of Colon Cancer
PhysicalActivity
Dietary Glycemic Index
Low Medium High
High 1.0 1.3 1.4
Medium 1.6 1.8 2.1
Low 1.5 1.9 3.5
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Other Protective Effects
Inhibitors of invasive processes – Stimulate plasminogen activator inhibitors
Reduces plasmin-stimulated degradation of extracellular membrane