Midterm 2 Flashcards
top 5 leading causes of death
- dieseas of the heat
- malignant neoplasma
- chronic lower respiratory disease
- cerebrovascular disease (stroke)
- accidents
Disease of the heart + Malignant neoplasms make up… % of deaths
50
women live longer than men but…
their cause of death from stroke or alzheimers disease is higher
top 5 leading causes of deaths for infants
- congenital malformations
- diorders related to short gestation and low birth weight
- suddan infant death syndrome
- newborn affected by maternal complications of pregnancy
- accidents
Death and the environment. 3 kinds of environments that effect
social, geological, biological
example of social environment and death
married, divorced, widowed differnet life expectnacies.
example of geography and death
different areas of the US have different life expectancies
example of biology and death
being male is a risk factor.
1 in 10,000 means
up to one additinal case from a designated cuase in a population of 10,000 people may occur in the next 70years
rate per person-time estimate
example: 10 people exposed to an adgent all worked for different number of yeats. estimate could be X/total of all persons years
estimated relavtive risk
incident rate in exposed/incident rate in non exposed. 1= no association. >1 positive correlation. <negative correlation
de minimis
society must accept some level of risk. threshold below risks are considered trivial. sometimes it is set lower if the benefit is great.
Top 3 underlying causes of death
- tobacco
- poor diet and physical activity
- alcphol consumption
DRI
dietary reference intakes. include EAR, RDA, AI and UL
EAR
estimated average requirment- average intake needed to prevent clinical deficiency
RDA
recommended daily allowance. calculated value (EAR + 2 SD)
AI
adequate intake. in absesnse of data provided an EAR and RDA. Mean intake of a healthy population
UL
upper tolerable level. highest safe intake where no signs of toxicity are evident.
how to estimate when a toxin becomes a hazard
dose response and exposure
NOAEL
No observed adverse effect level- hgighest concentration reported that doesn not cause harm
LOAEL
lowest concentration reporded that does not cause hardm
Estimated Exposure Dose, EED
measured or calculated dose to which humans are likelt to be exposed considering exposure from all other sources and routes.
Margin or exposure, MOE
ratio of the NOAEL and the EED
IPCS
International Programme on Chemical Safety. define “tolerable intake”
Tolerable Intake
lifetime intake of a substanct that can occur without appreciable health risk. TI= NOAEL/UF
UF
uncertainty factor
Interspecies UF
10^0.4 x 10^0.6
Intraspecies UF
10^0.5 x 10^0.5
Boron
widely used in consumer and construction products, an ingrediant in detergents, cosmetics, toothpast, glass and preservatives.
Critical Effect
An observable effect. example: Fetal rat weight. Dont want to chose death as critical effect.
Monitor types
Area monitors, Personnel monitors (radiation badges on indviduals), biomarkers
examples of potential intraspecific differences
fetus or child compared to adult- absorbtion, excretion, metabolism, body burden. male compared to fema, germ cell, developmental toxns. old compared to young- dermal absorption
Reference Dose
replaced the concept of acceptable daily intake to avoide the idea of “acceptabe” and “saftey”. RfD=NOAEL/UF
EPA criteria for evaluating carcinogenic potential
mode of action weight of toxicology evidence dose-response assessment susceptible populations and life-stages evaluation risk from childhood exposures characterizations of overal risk
Mode of Action
sequence of events and processes starting with interaction of an agent with cell. examples: mutagenicity, miogenesis, inhibition of cell death, cytotoxicity
Weight of Evidence
evidence of tumors in exposes animals or humans. chemical and physical properties. evidence hemical activates carcinogenic processes.
Risk assessment Carcinogens
non-caner toxins have threshold. carcinogens to not have thresholds! One moluecule is a risk.
Cancer slope factors
chemical/bodywight per exposure period
Cancer potency
95% upper confidence limit of the slope factor
Cancer risk
C x [(IR x EF e ED)/(BXxAT)]xSFxASF
c=concentration in mg/L IR=intake in L/day BW=body weight EF=exposure frequency ED=exposure duration in years AT=average time exposed SF=cancer slope factor ASF=age senstive factor
Risk Managment
science 30%
Law 30%
Politics 40%
HQ
Hazard Quotient- risk from exposure via a single pathway. EED/RfD
HI
Hazard Index- sum of all HQ
Politics of risk managment
familiar riska are less fearfull. unfamiliar risk are more feared
assessment of microbes
major differences from chemicals:
chemicals do not multiply
microbes multiply and undergo natural selection in host.
neoplasm
tumor
malignant
rapidly growing clones of the cells. cause cachexia(loss of apetite)
Bengign tumors- suffix
-oma. examples: fibroma= benign tumor of fibrous tissue.
carcin-
-oma
malignant tumor of the glands of the stomach
sarc-
-oma
maligmnant tumors of mesenchymal origin
VDPIMP
evaluate biopsy to determin if neoplasm is present
V-variation D-disorganization P-proliferation I-invasion M-metastasis P-persistence
ectoderm=
endoderm=
mesoderm=
carcinoma
carcinoma
sarcoma
Tumors are of monoclonal origin
the cell which initiates genesis of cancer is not itself malignant but the cells progeny
cancer risk is higher in populations exposed to certain chemicals
snuff causes cancer.
chromosomes are involved
chromosomal aberrations are consistently associated with various types of cancer
Ames test
testing for mutagenicity. environmental egents can cuase mutations.
Oncogenes
cancer genes. retroviral RNa0 can reverse transcribe into DNA and incorporant into the host DNA.
proto-oncogene
humans carry genes with that them that when damaged can cause cancer.
- control cell division
- control cell differentiation
- can aquire mutations that convert them into oncogenes
- oncogenes convernt normal cells into cancer cells
types of damage that can convert proto-oncogenes to oncogenes
- point mutations
- translocation
- gene amplification
Tumor suppressor genes
- control cell division
- DNA repair genes
- Apoptosis genes
Normal adult tissue control 3 cell processes
- continued replication
- differentiation to take on specialized functions
- apoptosis
Tissue Cell Number= Cell Proliferation - Cell Death
# of Cells = (oncogenes+damaged tumor suppressor) - damages apoptosis genes ... = CANCER
Familial Proportion of risk
environment plays a bigger role than genetics in cancer.
UV Light and Skin Cancer
UV radiation causes the formation of pyrimadine dimers in specific DNA sequences of the tumor suppressor gene. DNA synthesis will fix these mutations.
Benzo(a)pyrene (BaP)
byproduct of incomplete comustion of coal, wood, tobacco. cuased scrotal cancer in chimney sweeps. protective clohing provided the first successful progrm in cancer prevention.
HPV
the environmental agent in cervical cancer. HPV is very high risk factor for penile, vulvar and cervical cancer. strong link between APV and oral, larynx, esophogus and lung cancer.
Breast Cancer
terminal epithelial milk bulb is wear cancer occurs. ductus system greatly expands when pregnant, even more dense when breast feeding then stops and then apoptosis. becoming pregnant lowers risk for breast cance.r
Stem Cell Cancer Hypothesis
mutations that cause cancer occu in the stem cell or its progenitor cell.
Progenitor Cell
differentiate into different types of specialized cells.
common metals associated with cancer risk
- arsenic
- cadmium
- chromium
- nickel
Genotoxins
agents that cause DNA damage
nucleoside
pyrimidine or purine + ribose
nucleotide
nucleoside + phosphate
Transcription
DNA converted to mRNA
translation
mRNA to protein
example of environmental pollution and selection
shift in moth color correlated with the introduction of U.S. air pollution laws.
constitutional chromosomal aberraton
those that you are born with
acquired chromosomal aberration
arise as secondary changes to other diseases such as cancer.
Clastogenic damage
damage to chromosomes
deletion
loss of material from a singel chromosom
Inversions
2 breaks occur within a single chromosom and the broken segment flips and reattatches. usually no risk to individual if inversion is familial origin. slightly increased risk itf it is de novo (new).
Translocation
exchange of materials between 2 or more chromosomes. If is reciprocal (balanced)- risk for problems to an individual is similar to inversions (none if familial and slightly increased if de novo). If a gamete combines with a normal gamete, one is monosomic and one is trisomic.
Transition
purines exchanged of pyrimidines changed, but purine or pyrimadine oreintation remains the same.
Transversion
purine replaced with pyrimidine or vise versa.
The Ames Test
most widely used test for mutagenicity
Del Assay
Ames test doesnt detect mutations caused by the deletion of a gene. Del Assay does.
Cell Checkpoint System
arrests cells before DNA synthesis and again during chromosomal duplication to allow time for repair.
Nucleotide Excision Repair
NER- pathway is a system the removes a broad spectrum of structurally unrelated lesion such as UV induced photoproducts
Epigenetics
Above the Gene
The expression of genes can be turned off by
- addition of methyl groups on cytosine bases
- addition of methyl groups on histone proteins that surround DNA
- addition of acetyl groups to histones to cause them to tighten and make the grooves of DNA inacessible so that genes in a particular region cannot be expressed.
Some exposures that trigger epigenetics changes.
radiation
particle and non-particel electromagnetic energy that radiates from a source.
Natural Radiation
the neuron is unstable and decays. The instability explains why there is a natural radioactivity in our water supplies, soil and indoor air.
Ionizing Radiation
radiation that has enough energy to remove an electron from an atom. 5 major types:
- alpha
- beta
- X
- gamma
- neutron radiation
Quark
smallest unit of matter
Nuclear Radiation
emission of atomic particles from the nucleus of an atom.
Radionuclide
an atom whose nuclei is unstable and emits particles such as alpha or beta particles or electromagnetic radiation in the form of X or gamma
Atomic Mass
sum of the number of protons and neutrons in the nucleus of an atom
atomic number
number of protons in the nucleus of an atom
proton
a nuclear particle composed of 3 quarks that has a mass of 1 and charge of +1
Neutron
nuclear particel composed of 3 quarks that wighs as much as a proton but has no charge.
electron
an atomic particle that has a charge of -1. weighs 1/2000 of a proton
Isotopes
atoms with the same number of protons but different number of neutrons
Particulate Radiation
- particles have a defined range of matter rather than an absorption profile like electromagnetic waves
- particles undergo nuclear reactions to produce secondary particles
- particles deposit energy along well defined linear paths
Alpha particles
big and heavy, arise from unstable radioactive isotopes emitted from the nucleus of elements with mass number greater than 208.
He nuclei
Beta particles
no independent existence inside the nucleus. created at the instant of emission. emitted by unstable isotopes.
Non-particulate radiation
x=rays and y-rays. quanta of electromagnetic energy and no mass. they are highly penetrating and travel long distances through dense materials.
Health effects of radiation
due to the ionization proces (formation of ions). can be direct and indirect
direct
energy from free electron in an ionized atom trasnferred directly yo DNA or any other macromolecule to cause damage.
Indirect
energy from an electron of an ionized atom in the form of a photon is absorbed by one of the oxygen electrons in water. cuases the electron to rise to a higher lecel forming a radical.
Atomic Bomb radiaiton
children survivors developed more leukemia.
Chernobyl
developed more thyroid cancer. 40% of the population was suffereing from iodine deficiency at the time of the accident.
acute radiation symptoms
epilation, vomiting, bleeding from the gums, diarrhea and purpura.
Threshold Dose
below a certain radiation does, no acute symptoms occur, in contrast to a theory knwon as the linear dose-response relationship.
Fukushima
earthquake and tsumani 2011 resulted in the worst nuclear plant accident since Chernobyl. thousands of people exposed to cesium 134. scientists want to find out if there is a thresholf below which no ill effects exist.
non-ionizing radiation
electromagnetic waves that dont have enough energy to ionize atoms
Infared
see it when looking at a hot burner on an electrc stove. high enough energy to cause thermal burns.
UV light
causes amage through both thermal and photochemical mechanisms. The most common skin effect is erythema (reddening)
UV-A
degrades collagen and elastin. causes wrinkles. has been shown to cause melanoma.
UV-B
causes skin to thicken and harden. causes sunburn.
Vitamin D
foods do not contain vitamin D unless they are fortified.
UV-B sunscreen
can cause vitamin D deficiency. there is a balance between the amount needed for the synthesis of vitamin D and harmful levels that destroy folic acid.
ABCD
Asymmetrical shape
Borders that is irrefular or jagged
Color that varies from tan to brown to black or red to blue
Diameter bigger than the top of a pencil eraser
high-risk groups
people with red or blonde hair, more than 50 moles, three or more blistering sunburns in the past or a family history or melanoma.
neurotoxin
substance that damages neuron or cell types in the nervous system
neurobehavioral toxin
neurotoxins that change people behavior. nicotone and opiates.
neuropathy
death of neurons
axonopathy
neruonal axon is the primary site of injury, degnerates leaving just the cell budy
myelinopathy
disruption of the myelin
Gliosis
astrocytes, non-neronal cells in the brain proliferate in the space left by the death of neurons
Lead exposure comes from
lead based paint, battery recycling industry, old cooking vessels, ceramic paints, the wrappers of candy.
Lead in children
children blood levels inversley associated with IQ and positively associated with ADHD. can lead to seizure, coma and death
90% of lead deposited in
the mineral matrix of the skeleton. inhibits heme synthesis. increases blood pressuer and results in strokes. reduces male fertility
chronic Pb
peripheral motor weakness, impaired learning and low intelligence. severe headache, convulsion, coma, delirium and death.
25 ug/100ml Pb
reportaed to the health department
45 ug/100ml Pb
requires chelation therapy
65 ug/100ml Pb
hospitalize
how is lead different than other non-carcinogens?
toxic at all concentratons
Primary source of elemental mercury
coal burning power plants.
how does elemental mercury become methyl murcury?
concerted by bacteria, then bioaccumulates in the food chain.
primary source of Hg exposure comes from
Eating fish
Dental amalgam
50% elemental Hg. other materials dont work as well.
why is organic mercury toxic and elementay mercury is not?
the non-polar methyl groups increase lipid solubility allowing it to cross the bloob brain barrier. the more lipid soluble, the more toxic
recomendations for selecting and eating fish and shellfish (women and young children)
- do not eat shark, swordfish, king mackeral or tilefish
- low mercury=shrimp, canned una, salmon , poluck and catfish
- albacore tuna has more mercury than canned tuna.
Minimata Bay Japan
1953 plastic manufacture discharged into sea, 700 people dies, 9000 paralysis brain dead. 25% children had mental deficiency.
Iraq 1972
wheatseeds mercury fungicide, 65000 ill, 459 dead.
Adiction results from changes in 3 neuronal pathways:
- physical- autonomic and somatic function. physical dependence and withdrawl
- motivation-mesoaccumbens dopamine projections entending from ventral tegmental area of midbrain to nucleua accumbens
- associative memory systems that produce powerful learned associations , predispose drug cravings.
Reward pathway
release of neurotransmitter dopamine. dopamine release normally serves to reinforce behaviors that lead to biologically important rewards.
Tolerance
desensitivation of nicotine receptors
Sensitization
opposite of tolerance. faster highs with repeasted use of marijuana
Euphoria
the buzz, rush or high state of pleasure from a drug
Craving
the psychological desire for more of a drug
Smoking and the brain
effects populations differently. some populations are more resistant to smoking related cascular diesases.
Physiological effects of tobacco
vision, visual movement, endocrine function, blood pressure, motivation increase, emotion increase. 10 second delivery
Nicotine, how does it cause additiction?
ability to bind to the presynaptic receptiors in the CNS, activated reward system. binds to more receptors, maked unavailible for normal function- desensitivation. # of unbound receptors associated with depression.
Insula
proposed to function in coscious urge.
declarative v undeclarative learning
nndeclarative- skills, habits not accessible to a conscious mind.
Opiates addition at cellular level
reduce pain. ventral fragment areas release endogenous opioid peptides.
Marijuana at cellular level
endocannabinoids-bine to cannabinoid rceptors. decreased release of neurotransmitters affecting pain perception. affects memoryand cognition. increases apetite. observed to increase psychic breaks in students? Long term problem is dullness and lack of motivation.
Naegele’s Rule
subtract 3 months from the first day of the last perior and add one year and 7 days.
Reproductive toxin
chemicals that disrupt normal concenption, implantation and in vitro fertilization and prenatal development
Maternal weight gain during pregnancy…
outside the recommended ranges, associated with suboptimal maternal and childhealth. retain wight after delivery, more likely to undergo c-section and deliver large for gestational age newborns.
maternal constraint
fetal growth is matched with maternal size rather that genetic potential. mediated by placental size, perfusion og nutrients into the fetus, genetic expression of growth factors.
rate of preterm and low birthweight infants
8.1% of births
SGA
small for gestational age
IUGR
Intrauterine growth restriction- infants that have failed to reach their growth potential due to insult in utereo
preterm
infants born before their normal due date. (environmental toxins like tobacco, Pb, Cd increase risk)
oogonia
ova are formed in the ovary from these cells. arrected in the first stage of meiosis during embryogenisis. the second stae of meiosis is completed in the oviduct after sperm penetration.
atresia
follicular death. the number of oogonia is fixed at birth and not replaced overtime, they undergo XX
FSH
rise about 20 ng/ml= biomarker for onset of menopause
Torschlusspanik
panic felt by people when left outside city walls after gates close. now used in context of anxiety some women experience as their doors to reproductive years begin to close.
Grandmother hypothesis
menopause cuts of reproduction and keeps an adult female around to support her children and gradchildren.
Older males sperm
mutations in DNA increase with age. the ability to repair genetic damage diminishes with age. older males father more girls, sperm carrying Y chromosome are less hearty?
Impotency problems
50% of 50 year old men. 60% of 60…
Germ Cell Toxins
examples:lead and DCBP
DES- diethylstillbestrol
syntehstic estrogen that was used as an anti-abortive agent to prevent miscarrige in 1947-1070. 80% of female offspring developed glandular epithelium. and increased risk of some cancers
Puberty
kisspeptin and receptor GPR54 “kiss”, prepare body for sexual maturity.
increased trend for earliist breast development and menarche
most likely explanation= trend of increase in body weight and obesity.
Implantation
morula–> blastocyst —> attatches to uterine epithelium—> implants in the uterine lining (durng window of implantation, opened by surge of estrogen)
organogensis
cell proliferation and differentiation from a pattern of the organ structure. distruption of this process can stop development of an organ or make it disfunctional.
teratogen
a chemical that causes a birth defect
most sensitive period of gestation
implantation and organogensis
Thalidomide
a sedative used to prevent morning sickness panned in 1961- discovered to impair limb bud formation. its antiangiogensis properties make it a good for treated leprosy and muscular degeneration.
DBCP
soil fumigant in 1960s and 1970s pesticide. testicular toxin. degeneration of sminiferous tubules, lead to low sperm counts, abnormal sperm and aspermia.
endocrine disruptors
chemicals that alter normal hormone function.
estrogen and antiestrogen
estrogen circulates in the blood, environmental agents bind to estrogen receptors, acts as an agonist, stimulates the receptor.
common endocrine disruptors
DES, dioxin, PBCs, DDT. maybe DDE, BPA,phthalats
endometriosis
endometrium grows in other places, fallopian tubes, ovaries ect. inflammatory response, can cut off blood supply to an ovary.
Stress hypothesis
ancient biological response to danger. male pregnancies are more likley to miscarry in response to stree than female pregnancies. low blood glucose levels in women favor daughters. birth of more females concienved furing famine beneficial outcome.
