SKIN 6131 Flashcards by doinke zzzz

Q

protects the body against external insults in order to maintain
internal homeostasis

A

skin

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Q

Skin is _______ of our body mass

A

10%

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Q

Skin is the most accessible organ in the body (t or f)

A

T

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Q

It participates directly in ________, _________, ________, ________, and _________

A

thermal, electrolyte, hormonal,
metabolic, and immune regulation

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Q

Thick stratum
corneum—good physical
barrier
Common site of contact with
chemicals
Occlusion with protective
clothing

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Palm/soles

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Q

Moist, occluded areas
Chemical trapping
Enhanced percutaneous
absorption

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Intertriginous areas

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Q

example of Intertriginous areas

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

axillae, groin, neck, finger webs, umbilicus, genitalia

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Q

Exposed frequently
Surface lipid interacts with
hydrophobic substances
Chemicals frequently
transferred rom hands

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Face

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Q

Poor barrier function—thin
epidermis
Sensitive to irritants

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Eyelids

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Q

Chemical trapping
Occlusion

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Postauricular region

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Q

Chemical trapping
Hair follicles susceptible to
metabolic damage

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Scalp

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Q

Increased sensitivity to
irritants
Impaired barrier function

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Atopic dermatitis

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Q

Impaired barrier function

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Psoriasis

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Q

Predisposition to skin
disorders
Variation in sensitivity to
irritants
Susceptibility to contact
sensitization

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Genetic Factors

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Q

Vasodilation—improved
percutaneous absorption
Increased
sweating—trapping

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Temperature

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Q

Increased
sweating—trapping

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Humidity

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Q

Variation in relative humidity
Chapping and wind-related
skin changes

(FACTORS INFLUENCING CUTANEOUS RESPONSES)

A

Season

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Q

Two major components of the skin that are separated by a basement membrane

A

epidermis and underlying dermis

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Q

Thickness of dermis

A

approximately 90% of the skin (has largely a supportive function)

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Q

span the epidermis and are embedded in the dermis

A

epidermal appendages

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Q

examples of epidermal appendages

A

Hair follicles
Sebaceous glands
Eccrine glands

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Q

Layer that separates the dermis from underlying tissues

A

adipocytes

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Q

Accumulation of fat has a cushioning action

A

adipocytes

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Q

Somehow regulates our body temperature

A

adipocytes

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Supply the bulbs of the hair follicles and the secretory cells of the eccrine (sweat) glands.

Capillaries

The ducts from these glands carry a dilute salt solution (that is sweat) to the surface of the skin, where its evaporation provides cooling sensation.

capillaries

Stratified squamous epithelium consisting primarily of keratinocytes

Interfollicular epidermis

Interfollicular epidermis is a stratified squamous epithelium consisting primarily of __________

keratinocytes

stimulated by ultraviolet light in the epidermis to produce melanin granules which are extruded and taken up by the surrounding keratinocytes and become pigmented

melanocytes

Widely distributed in the dermis, with occasional concentrations beneath the basal lamina and in the papillae of hair follicles

Melanocytes

Dendritic, antigen-presenting cells usually involved in the immune response of skin to foreign agents, particularly to xenobiotics

Langerhans cells (LCs)

Keratinocytes of the ___________ make up the germinative compartment

basal layer

- Cells become flattened and increase in volume nearly 40-fold. - Lipid granules fuse with the plasma membrane, replacing the aqueous environment in the intercellular space with their contents.

Granular Layer

- Plasma membranes of these cells become permeable and cell organelles are degraded, while a protein envelope is synthesized immediately beneath the plasma membrane.

Granular layer

Begins as keratinocytes leaving the basal layer, producing the outermost layer of the skin, the stratum corneum.

Terminal Differentiation

- Mature cells - No longer viable - ~80% keratin in content - They are gradually shed from the surface and replaced from beneath

Corneocytes

process typically takes 2 weeks or basal cells to reach the stratum corneum and another 2 weeks to be shed from the surface

Terminal Differentiation

When a basal cell divides, one of the progeny detaches from the basal lamina and migrates outward. Usually moves towards the skin surface

Terminal differentiation

The primary barrier to percutaneous absorption

Stratum corneum

the stratum corneum is formed during the process of ___________

terminal differentiation

the stratum corneum has _________ properties which prevents water loss from underlying tissues by evaporation

Hydrophobic

The SC is ordinarily hydrated which contains around ____ water or the moisture residing in corneocyte protein

20%

The lipids, a major component being ________, have a high content of long-chain ceramides removal of which seriously compromises barrier function as measured by TEWL

sphingolipids

Two intrinsic factors which contributes to the absorption rate of a given compound

- Hydrophobicity - Rate of Diffusion through this barrier

- Affects its ability to partition into epidermal lipid, and its rate of diffusion through this barrier - Usually computed using the octanol/water partitioning ratio

Hydrophobicity

↑ Kow = ____________

hydrophobic

Partitioning of an agent into the skin is greatly affected by its solubility in or adhesion to the medium in which it is applied (including soil) (t or f)

T

hydrophobic compounds, once in the SC, may diffuse rapidly into less hydrophobic regions below (t or f)

F; very slowly

Hydrophobic substances with low MW permeate the skin better than those with high MW or those that are hydrophilic. (t or f)

T

A list in order of decreasing permeability under steady-state conditions gives the following hierarchy

foot sole > palm > scrotum > forehead > abdomen

Absorption through the epidermal appendages is generally neglected because the combined appendageal surface area is a small fraction of the total available area for the absorption (t or f)

T

Advantages of transdermal drug delivery

- Provides a steady infusion or extended periods (typically 1 to 7 days) thereby avoiding large variations in plasma concentration - Preventing exposure to the acidic pH of the stomach - Avoid biotransformation in the gastrointestinal tract or from first-pass removal by the liver

For risk assessment and pharmaceutical design, the most useful subject or experimentation is ___________ (Measurement of Penetration)

human skin

human skin is always used for clinical trials (t or f) (Measurement of Penetration)

T

Human skin can also be used for pre-clinical trials (t or f) (Measurement of Penetration)

F

For in vitro work, _______________ can be employed in special diffusion chambers, though care is needed to preserve the viability of the living layer of epidermis. (Measurement of Penetration)

excised split-thickness skin

A simpler setup commonly employed uses ____________ skin with the lower dermis removed. (Measurement of Penetration)

cadaver

No life. Lacks biotransformation capability but retains the barrier function of the SC (Measurement of Penetration)

Cadaver skin

To simplify determination of penetration kinetics, __________ may be employed and the _____________ monitored to measure penetration. Pig skin may be used (Measurement of Penetration)

skin flaps; capillary blood flow

The major sites of biotransformation or metabolism of the skin is the _________ and __________ of the skin.

epidermis; pilosebaceous units

Enzymes participating in the biotransformation that are expressed in the skin

- CYP450 - epoxied hydrolase - UDP glucuronosyltransferase - Quinone reductase - Glutathione transferase

Other metabolic enzyme activities detected in human epidermal cells include:

- Sulfatases - β-glucuronidase - N-acetyltransferases - Esterases - Reductases

The intercellular region of the stratum corneum has catabolic activities.....

- proteases - lipases - glycosidases - phosphatase

- Common skin disorder - Accounts or over 90% of reported causes (of all occupational skin disease) - involve in inflammatory processes and can have indistinguishable clinical characteristics of erythema (redness), induration (thickening and firmness), scaling (flaking), and vesiculation (blistering) on areas directly contacting the chemical agent.

Contact dermatitis

two types of contact dermatitis

- irritant - allergic both may co-exist

- Arises from the direct contact of agents on the skin at a higher concentration or longer exposure - Certain chemicals at sufficient concentration produce an acute irritation, sometimes called a second-degree chemical burn.

Irritant dermatitis

- It can be produced by strong acids, alkalis, and powerful oxidizing or reducing agents can substantially disrupt the cornified layer, producing cytotoxicity directly

Irritant dermatitis

Contact with a variety of plants can also have irritant effects resulting in the production of proinflammatory cytokines like

IL1a, IL1B, and TNFa from keratinocytes

the back is more sensitive than the forearm (t or f)

T

____________ are the most sensitive to irritants and exhibit a propensity to produce specific IgE antibodies to allergens and typically suffer from hay fever

Atopic individuals

- Extremely corrosive and reactive chemicals may produce immediate coagulative necrosis that results in substantial tissue damage

Chemical burns

Manifestations of chemical burns

Ulceration and Sloughing

Chemical burns are sometimes referred to as ___________

Third degree burns

____________ can act as a chemical reservoir resulting in either continued cutaneous damage or percutaneous absorption and systemic injury after exposure

Necrotic tissue

- Potent skin corrosive - Contact with compressed gas can cause frostbite (SELECTED CHEMICALS CAUSING SKIN BURN)

Ammonia

- Severe chemical burns - Extremely exothermic reaction—dissolving in water can cause heat burns (SELECTED CHEMICALS CAUSING SKIN BURN)

Calcium Oxide (CaO)

- Liquid and concentrated vapors cause cell death and ulceration (SELECTED CHEMICALS CAUSING SKIN BURN)

Chlorine

- Solutions and vapors may burn - Compressed gas can cause frostbite (SELECTED CHEMICALS CAUSING SKIN BURN)

Ethylene oxide

Severe burning with scar formation (SELECTED CHEMICALS CAUSING SKIN BURN)

Hydrogen chloride (HCl)

- Severe, painful, slowly healing burns from high concentration - Lower concentration causes delayed cutaneous injury - Systemic absorption can lead to electrolyte abnormalities and death - Calcium-containing topical medications and quaternary ammonium compounds are used to limit damage (SELECTED CHEMICALS CAUSING SKIN BURN)

Hydrogen flouride (HF)

High concentration causes severe burns and blistering (SELECTED CHEMICALS CAUSING SKIN BURN)

Hydrogen peroxide

Liquid exposure produces blistering, deep burns (SELECTED CHEMICALS CAUSING SKIN BURN)

Methyl bromide

Moist skin facilitates the formation of nitric acid causing severe yellow-colored burns (SELECTED CHEMICALS CAUSING SKIN BURN)

Nitrogen oxides

White phosphorus continues to burn on skin in the presence of air (SELECTED CHEMICALS CAUSING SKIN BURN)

Phosphorus

- Extremely corrosive even in low concentrations - Systemic absorption through burn sites may result in > Cardiac arrhythmias, Renal disease, and Death (SELECTED CHEMICALS CAUSING SKIN BURN)

Phenol

High concentration causes deep burns, readily denatures keratin (SELECTED CHEMICALS CAUSING SKIN BURN)

Sodium hydroxide

- Severe burns with contact - Skin contact rarely may result in respiratory sensitization (SELECTED CHEMICALS CAUSING SKIN BURN)

Toluene diisocyanate

is a delayed (T-cell mediated) hypersensitive reaction (SELECTED CHEMICALS CAUSING SKIN BURN)

Allergic contact dermatitis

Unlike contact irritants where the response is generally proportional to applied dose and time, contact allergens can elicit action even at small doses (t or f)

T

To induce sensitization, ______________ must penetrate the skin and become attached to carrier proteins (ALLERGIC CONTACT DERMATITIS)

chemical haptens

complete antigens are processed by ____________ and presented to ___________ in regional lymph nodes

Langerhans cells; type 1 -helper cells

Subsequent exposure to the same antigen results in an amplified immune response characterized by ____________ and ____________

dermal infiltration; spongiosis

Topical medications/hygiene products (COMMON CONTACT ALLERGENS)

- Antibiotics - Therapeutics - Preservatives - Others

- Bacitracin - Neomycin - Polymyxin - Aminoglycosides - Sulfonamides (COMMON CONTACT ALLERGENS)

Under antibiotics

- Benzocaine - Idoxuridine - α-Tocopherol (vitamin E) - Corticosteroids (COMMON CONTACT ALLERGENS)

Under therapeutics

- Benzalkonium chloride - Formaldehyde - Formaldehyde releasers - Quaternium-15 - Imidazolidinyl urea - Diazolidinyl urea - DMDM hydantoin - Methylchloroisothiaolinone (COMMON CONTACT ALLERGENS)

Under Preservatives/personal care products

- Cinnamic aldehyde - Ethylenediamine - Lanolin - p-Phenylenediamine - Propylene glycol - Benzophenones - Fragrances - Thioglycolates (COMMON CONTACT ALLERGENS)

Under Other topical medications and hygiene products

- Abietic acid - Balsam of Peru - Rosin (colophony) - Pentadecylcatechols - Sesquiterpene lactone - Tuliposide A (COMMON CONTACT ALLERGENS)

Under Plants and trees

- Chloramine - Chlorhexidine - Chloroxylenol - Dichlorophene - Dodecylaminoethyl glycine HCl - Glutaraldehyde - Hexachlorophene - Thimerosal (Merthiolate) - Mercurials - Triphenylmethane dyes (COMMON CONTACT ALLERGENS)

Under Antiseptics

- Diphenylguanidine - Hydroquinone - Mercaptobenzothiazole - p-Phenylenediamine - Resorcinol monobenzoate - Benzothiazole sulfenamides - Dithiocarbamates - Thiurams (COMMON CONTACT ALLERGENS)

Under Rubber products

- Formaldehyde - Glutaraldehyde - Potassium dichromate (COMMON CONTACT ALLERGENS)

Under Leather

- Abietic acid - Formaldehyde - Nigrosine - Rosin (colophony) - Triphenyl phosphate - Dyes (COMMON CONTACT ALLERGENS)

Under Paper products

- Bisphenol A - Epichlorohydrin - Formaldehyde - Acrylic monomers - Cyanoacrylates - Epoxy resins - p-(t-Butyl) formaldehyde resin - Toluene sulfonamide resins - Urea-formaldehyde resins (COMMON CONTACT ALLERGENS)

Under Glues and bonding agents

- Chromium - Cobalt - Mercury - Nickel (COMMON CONTACT ALLERGENS)

Under Metals

Chemical: Abietic acid (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Pine resin (colophony)

Chemical: Balsam of Peru (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Pine resin, cinnamates, benzoates

Chemical: Bisphenol A (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Diethylstilbestrol, hydroquinone monobenzyl ether

Chemical: Canaga oil (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Benzyl salicylate

Chemical: Chlorocresol (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Chloroxylenol

Chemical: Diazolidinyl urea (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Imidazolidinyl urea, ormaldehyde

Chemical: Ethylenediamine di-HCl (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Aminophylline, piperazine

Chemical: Formaldehyde (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Arylsulfonamide resin, chloroallylhexaminium chloride

Chemical: Hydroquinone (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Resorcinol

Chemical: Methyl hydroxybenzoate (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Parabens, hydroquinone monobenzyl ether

Chemical: p-Aminobenzoic acid (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: p-Aminosalicylic acid, sulfonamide

Chemical: Phenylenediamine (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Parabens, p aminobenzoic acid

Chemical: Propyl hydroxybenzoate (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Hydroquinone monobenzyl ether

Chemical: Phenol (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Resorcinol, cresols, hydroquinone

Chemical: Tetramethylthiuram disulfide (COMMON CROSS-REACTING CHEMICALS)

Cross-reactor: Tetraethylthiuram mono- and disulfide

is one in which invading substances that cannot be readily removed are consequently isolated.

Granulomatous reactions

- Silica - Talc (Seen in powders) - Paraffin or mineral oil - Beryllium - Gadolinium - Metallic mercury and zirconium compounds - tattoo dyes (containing cobalt, chromium, mercury, lead, iron, cadmium, and manganese compounds)

substances that may produce granuloma

UV and visible spectra of solar radiation reaching the earth extend from

290 to 700 nm

wavelength of UV-C

< 290 nm

wavelength of UVB

290-320 nm

The protective skin pigment melanin, synthesized in melanocytes, absorbs a broad range of radiation from

UV-B

Other chromophores in the skin include amino acids, primarily _________ and to a lesser extent ________, and their breakdown products (e.g., urocanic acid), which absorb light in the UV-B range.

tryptophan; tyrosine

Biologically, the most significant chromophore in the skin is ________ since damage from radiation can have lasting effects on the genetic information in target cells.

DNA

Most evident acute feature of UV radiation exposure is ___________.

erythema (redness or sunburn)

Pigmentary changes - Freckling and hypomelanotic areas - Wrinkling - Telangiectasias (fine superficial blood vessels) - Actinic keratoses (precancerous lesions) - Malignant skin lesions such as basal and squamous cell carcinomas and malignant melanomas

Chronic exposure to radiation

- From exogenous chemicals may be produced by systemic or topical administration or exposure.

Phototoxicity

Phototoxic reactions may be produced either by systemic or topical exposures (t or f)

T

the skin may appear red and blister within minutes to hours after ultraviolet light exposure, particularly UV-A (320 to 400 nm) (PHOTOTOXICITY)

Acute exposure

responses may result in hyperpigmentation and thickening of the affected areas (PHOTOTOXICITY)

Chronic reactions

is the most commonly responsible for phototoxicity (wavelength)

UV-A (320 to 400 nm)

may occasionally be involved (wavelength)

UV-B (290 to 320 nm)

- 8-Methoxypsoralen - 5-Methoxypsoralen - Trimethoxypsoralen (SELECTED PHOTOTOXIC CHEMICALS)

Furocoumarins

- Anthracene - Fluoranthene - Acridine - Phenanthrene (SELECTED PHOTOTOXIC CHEMICALS)

Polycyclic aromatic hydrocarbons

- Tetracyclines - Sulfonamides - Sulfonylureas - Nalidixic acid - Thiazides - Phenothiazines - Nonsteroidal anti-inflammatory drugs (SELECTED PHOTOTOXIC CHEMICALS)

Drugs

- Disperse blue 35 - Eosin - Acridine orange (SELECTED PHOTOTOXIC CHEMICALS)

Dyes

- Hematoporphyrin (SELECTED PHOTOTOXIC CHEMICALS)

Porphyrin derivatives

is a type IV delayed hypersensitivity reaction, leading typically to eczema

Photoallergy

Photoallergy requires prior sensitization to the chemical. (t or f)

T

________ is necessary to convert a potential photosensitizing chemical into a hapten that elicits an allergic response

UV light

Pleomorphic disease with a multifactorial etiology

Acne

- The influence of sebum, hormones, bacteria, genetics, and environmental factors is well known. - Additionally papules, pustules, cysts, and scars may complicate the process.

Acne

- One of the most disfiguring forms of acne in humans - Caused by exposure to polyhalogenated aromatic hydrocarbons

Chloracne

Chloracne is a common disease; however, its recalcitrant nature and preventability make it an important occupational and environmental illness. (t or f)

F; Relatively rare

Pigmentary disturbances can be classified into....

hyperpigmentation or hypopigmentation

- results from increased melanin production or deposition of endogenous or exogenous pigment in the upper dermis. - can arise from deposition of metals and drugs in dermal tissue

Hyperpigmentation

is a loss of pigmentation from melanin loss, melanocyte damage, or vascular abnormalities.

Hypopigmentation

Denote complete loss of melanin from the skin, imparting a porcelain-white appearance

Leukoderma (vitiligo) and depigmentation

May develop for those allergens to which IgE antibodies have been elicited by previous or ongoing exposure, subsequent contact can lead to development of __________ (hives), typically in minutes, through an immediate type I hypersensitivity reaction

urticaria

are raised wheals that usually itch or sting and may appear reddish.

uticaria

are major causes of acute urticaria

food allergies and pharmaceuticals

- Rare, life-threatening disease - Represents one of the most life-threatening dermatologic diseases that is caused by drugs and chemicals. - Involves detachment of ≥ 30% of the epidermal surface from the dermis, commonly accompanied by severe erosions of mucous membranes

Toxic Epidermal Necrosis (Ten)

TEN commonly resembles an upper respiratory tract infection in the in the second month (fever, cough, sore throat, and malaise) (t or f)

F; first several days

Mucous membrane involvement can result in ...... (TOXIC EPIDERMAL NECROSIS (TEN))

gastrointestinal hemorrhage, respiratory failure, ocular abnormalities, and genitourinary complications

Nearly 200 drugs have been reported to cause this syndrome with major contributors being:

- anticonvulsants, - nonsteroidal anti-inflammatories - antibacterial - sulfonamides, - allopurinol, - nevirapine.

Radiation from ________ wavelengths to _________ wavelengths has been shown to cause skin cancer

ionizing; ultraviolet

Shortly after the discovery of radioactive elements at the turn of the twentieth century, it was observed that X-rays could cause:

- severe burns - squamous cell carcinoma - basal cell carcinomas

X-ray-induced nonmelanoma skin cancers (NMSC) continued to be observed throughout the twentieth century, as X-rays were used therapeutically until the mid-twentieth century or a variety of skin diseases such as

acne, atopic dermatitis, psoriasis, and tinea

Although NMSC from X-rays are now uncommon, __________ or ________ still is seen as sequelae of radiodermatitis, which sometimes develops after X-ray treatment of internal malignancies.

dermal atrophy or sclerosis

Most skin cancers in the US are now ___________

UV-induced

Most common UV-induced skin cancers are:

NMSC and cutaneous malignant melanoma

The _____ tumor suppressor gene has been targeted in nearly all squamous cell carcinomas

p53

Substances rich in polycyclic aromatic hydrocarbons _______________ are skin carcinogens in humans and animals.

coal tar, creosote, pitch, and soot

Oxidative biotransformation of polycyclic aromatic compounds produces ___________ that can form DNA adducts

electrophilic epoxides

_______ produced by rearrangement of the epoxides, can be oxidized further to ________, yielding active oxygen species, and they are also toxic electrophiles.

Phenols; quinones

has been developed as an important target for carcinogenicity testing.

Mouse skin

Advantage of the mouse skin carcinogenesis model

Ability to separate the neoplastic process into stages of initiation, promotion, and progression depending on experimental design.

Abundant element in the earth’s crust that is encountered routinely in small doses in the air, water, and food.

arsenic

High exposures from smelting operations and from well water derived from rock strata with a high arsenic content are associated with:

- arsenical keratoses (premalignant lesions), - black-foot disease (a circulatory disorder reflecting endothelial cell damage), - squamous cell carcinoma of the skin and several other organs (bladder, lung, and liver)

(+ 3 oxidation state) avidly binds vicinal thiols and is thought to inhibit DNA repair

Arsenite

(+ 5 oxidation state) can replace phosphate in macromolecules such as DNA, but the resulting esters are unstable.

Arsenate

________ also alters DNA methylation, suppresses keratinocyte differentiation markers, and enhances growth factor secretion in the epidermis.

Arsenic

_____________ has been considered the most likely detoxification method, because the observed mono- and dimethyl arsenate isolated in urine from exposed humans and animals are indeed much less toxic.

Methylation