Sunscreen

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Action of UV radiation on cellular biomolecules

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Sun light - skin

Chronic exposure to sunlight causes damage to the skin including erythema, edema, hyperplasia, formation of sunburn cells, photoaging, Suppression of the immune system skin cancer.

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Roles of UV radiation to human

UV Light
UV-A (320-400 nm) longer wavelengths

roles
formation of Vitamin D Penetrates deeper into the skin a major contributor to skin damage photoaging not filtered by glass

UV-B (290-320 nm) Shorter wavelengths

affects the outer layer of skin, the epidermis, responsible for sunburns presents risk to the development of cutaneous neoplasm.
Almost

UVC (100-290 nm)

totally blocked by the ozone

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layer, found in mercury arc lamps and germicidal lamps.

Damaging Effects of UVA and UVB

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UV radiation-skin damage

UV radiation Free Radicals can cause the secondary molecule to become a reactive, unstable free radical free radical chain reaction of molecular destabilization damage Lipids damage cell structures proteins (fibroblasts : the cells responsible for collagen and elastin production) slowed collagen and elastin less efficiently producing the skin protein necessary for skin smoothness, firmness, and elasticity Photo-aging Mitochondria poor cell renewal,

DNA cancer

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The epidermis

The epidermis consists of three types of cells keratinocytes, melanocytes and Langerhans cells. Keratinocytes, the predominant type of cells in the epidermis. Stratum corneum consists mainly of dead keratinocytes, hardened proteins (keratins) and lipids, forming a protective crust. Melanocytes, the cells producing melanin, the pigment responsible for skin tone and color. Langerhans cells are essentially a forepost of the immune system in the epidermis. They prevent unwanted foreingn substances from penetrating the skin.
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Electromagnetic radiation

GEK2500 Living with Chemistry

"People use mobile phones without thinking twice what the consequences might be. "It is just like using a toothbrush, but mobiles could be having a devastating effect on fertility. "It still has to be proved, but it could be having a huge impact because mobiles are so much part of lives." He suggested radiation from mobile phones might harm sperm by damaging DNA, September 2008 (Swedish study): affecting the cells in the testes which produce testosterone or the tubes where sperm is produced. But a British expert cast doubt the suggested linkbrain between mobile phone use and Children at on risk of future infertility in the men studied.

cancer if they are heavy users of Dr Allan Pacey, senior lecturer in andrology at the University of Sheffield, said: "This mobile phones

is a good study, but I don't think it tackles the issue. "If you're using your phone for four hours a day, presumably it is out of your pocket for Cf. several past studies longer. "That raises a big question: how is it that testicular damage is supposed to be occur?" Dr Pacey, who is honorary secretary of the British Fertility Society, added: "If you are holding it up to your head to speak a lot, it makes no sense that it is having a direct effect on your testes." He added that people who use phones for longer might be more sedentary, more GEK2500 Living with stressed or eat more junk food, which might be more likely explanations forChemistry the link

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UV exposure molecular damage

Some of the molecular events that occur in cells following UV exposure are DNA damage, induction of p53 and p53-regulated proteins, cell cycle arrest, DNA repair, apoptosis. UV induced DNA damage causes an elevation of p53 expression and p53 protein is translocated to the nucleus to regulate its downstream genes

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skin cancer development

Two pathway involves the action of UV on target cells: keratinocytes for neoplastic transformation, the hosts immune system

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UV can also induce apoptosis to order cells containing damaged DNA to self-destruct. It has been shown that UV-induced apoptosis is p53dependent In addition, UV radiation causes immuno suppression that may contribute to the emergence of skin tumors. Immune suppression results from the induction of suppressor T cells, either by damaged Langerhans cells or inflammatory macrophages that enter the skin following UV exposure
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Sunscreen

Sunscreen is a product that is supposed to protect the skin from the sun's ultraviolet (UV) radiation. The most effective sunscreens protect against both UVC (100-290 nm) totally blocked by the ozone layer UVB (280 and 320 nm) which encourage the formation of
melanin and lead to an immunosuppressant effect

(responsible for sunburn and basal and squamous cell carcinoma). UVA (320 and 400 nm), which penetrates the horny layer
and reach the epidermis and dermis.(responsible for

tanning, wrinkling, and melanoma) UV overexposures resulting in more long-term effects, such as premature skin aging. Epidemological studies shown that the sunscreen-user has a higher risk of skin cancer than the non-user safety? 18 Sri Noegrohati, GMU

Sunburn and malignant melanoma

statistical correlation exists between the number of sunburns and the risk to develop melanoma. cases of malignant melanoma in healthy humans originate from direct DNA damage only in 8% indirect DNA damage in 92 % Since the direct DNA damage is connected to sunburn it can be said that sunburn causes only 8 % of the melanoma cases and the indirect DNA damage (which is often amplified by sunscreen because it penetrates into the skin) is responsible for 92 % of all melanoma cases. (Indirect DNA damage is caused by reactive oxygen species (ROS), oxidative stress and free radicals)
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UVB exites DNA: adjacent thymine bases formed thymidine dimers distortion of DNA helix mutation cancerous growth
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Indirect DNA damage

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Comet assay (single cell gel electrophoresis (SCG)

a microgel electrophoresis technique which detects DNA damage and repair in individual cells. The damage is represented by an increase of DNA fragments that have migrated out of the cell nucleus in the form of a characteristic streak similar to the tail of a comet.

The DNA fragments are generated by DNA double strand breaks, single strand breaks and/or strand breaks induced by alkali-labile sites in the alkaline version of the assay. The length and fragment content of the tail is directly proportional to the amount of DNA damage
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cis-UCA formation

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ROS formations

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Antioxydant enzymes

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Pigmentation

UV radiation is the most significant factor influencing human skin pigmentation. As a direct effect of UV, especially UVA, immediate pigment darkening occurs within minutes and persists for several hours followed by persistent pigment darkening, which occurs within several hours and lasts for several days Melanocytes can produce three distinct kinds of melanins: two types of eumelanin, which are the predominant pigments found in dark skin and black hair, and pheomelanin, which is associated with the red hair/freckled skin phenotype. The type(s) of melanin produced depends on the function of melanogenic enzymes and the availability of substrates. pigmentation do not result from acute melanin synthesis but rather from the oxidation and polymerization of existing melanin and the redistribution of existing melanosomes.
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BIOSYNTHESIS OF MELANIN
Melanosit
(lapisan GERMINATIF)

melanosoma
TIROSINASE

tyrosin
INDOL-5,6-KINON
POLIMERISASI OKSIDATIF

dopa
DOPAKINON

(3,4-DIHIDROKSIFENILALANIN) DOPAOKSIDASE

MELANIN

TRANSFER DENDRIT MELANOSITIK

SEL MALPIGHI

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Schematic diagram of the tyrosinase processing and degradation pathway.

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Melanin synthetic pathway and the involvement of melanogenic enzymes.

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SC, stratum corneum; G, stratum granulosum; S, stratum spinosum; B, stratum basale; BM, basement membrane; D, dermis. Cell types: K, keratinocyte; M, melanocyte; F, fibroblast; shaded oval, melanin granule

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Sunscreen ingredients vs. melanin

Melanin has an extremely efficient photoprotective mechanism dissipates the energy from the UVradiation as harmless heat (internal conversion: more than 99.9 % of the energy is dissipated as heat) crucial to avoid the indirect DNA damage. does not act as a photosensitizer Sunscreen ingredients (e.g.: PABA, Benzophenone or Coumarin) do not posses this photoprotective property do not dissipate the absorbed energy efficiently photosensitizers starting indirect DNA damage should not be used in sunscreens?

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Sri Noegrohati, GMU

SC, stratum corneum; G, stratum granulosum S, stratum spinosum; B, stratum basale; BM, basement membrane D, dermis. Cell types: K, keratinocyte; M, melanocyte; F, fibroblast; shaded oval, melanin granule 35

International SPF, 2003, (Colipa, CTFA-SA, JCIA)

Number of test subjects 10 to 20 valid results Test area: Back (between scapula and waist) Reference/Standard products: 8% Homosalate SPF 4.2 (3.8 4.7) Amount of product applied: 2 mg.cm- 2.5% Space between test sites ; 1 cm between test sites at least 0.8 cm between sub-sites Light source : Xenon (+ WG320 + UG11 /1mm) Skin response; Erythema Observation time (post-exposure) 20 4 hours post-exposure Avoid extra-exposure of the back.

SPFi = MEDpi / MEDui

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Melanoma

is a malignant tumor of melanocytes which are found predominantly in skin, but also in the eye (uveal melanoma involving the iris, ciliary body, or choroid). It is one of the rarer types of skin cancer but causes the majority of skin cancer related deaths The tumor-suppressor protein p53 accumulates when DNA is damaged due to a chain of biochemical reactions. Part of this pathway includes interferon-alpha and interferon-beta, which induce transcription of the p53 gene and result in the increase of p53 protein level and enhancement of cancer cellapoptosis.[34] p53 prevents the cell from replicating by stopping the cell cycle at G1, or interphase, to give the cell time to repair, however it will induce apoptosis if damage is extensive and repair efforts fail. Any disruption to the regulation of the p53 or interferon genes will result in impaired apoptosis and the possible formation of tumors.
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Apoptosis

Apoptosis is a form of programmed cell death in multicellular organisms. Apoptosis and necrosis are sometimes very difficult to distinguish as both are characterised by damage of DNA leading to cell death. But because DNA damage can be caused naturally or by artificial mechanism ie introduction of intercalating agent, UV radiation, it will be easy to denote apoptosis as a suicidal event (cell own killing) while necrosis will be attributed the notation of cell death by injury (murdered cell). Recent studies on have demonstrated different steps of cell dying by necrosis or apoptosis

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P53

known as protein 53 (TP53), is a transcription factor that regulates the cell cycle and hence functions as a tumor suppressor. It is important in multicellular organisms as it helps to suppress cancer. located in the nucleus of cells throughout the body and can bind directly to DNA. p53 has many anti-cancer mechanisms: It can activate DNA repair proteins when DNA has sustained damage. It can also hold the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle.) It can initiate apoptosis, the programmed cell death, if the DNA damage proves to be irreparable

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DNA repair

When the DNA in a cell becomes damaged by agents such as toxic chemicals or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the cell will undergo programmed cell death (apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, the p53 tumor protein prevents the cell from dividing and signals it to undergo apoptosis.

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Some active ingredients in sunscreens

Benzyl salicylate and salicylate derivitaves, provides UVB protection, but not UVA. Benzyl cinnamate and cinnamate derivatives, an effective UVB blocker. PABA (p-aminobenzoic acid) may developed allergic reactions. Butyl methoxydibenzoylmethane and related compounds (Parsol 1789 and Parsol A) is an effective UVA blocker. Oxybenzone is a related compound. Zinc oxide and titanium dioxide are two inorganic compounds that block and reflect the UV radiation

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Estimation of the systemic intake of UV filters

Estimation of the systemic intake of UV filters via the skin from skin care and sun protection products depends on e.g. the frequency of application of products containing UV filters, the amount used, the relative amount of the filter(s), the filter combination and the galenics of the formulation as well as the ability of the UV filters to penetrate the skin.

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Comparation of MOS of UV filters in sun protection product and lipstick containing the same UV filters

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ANNEX VII: List of some permitted UV filters

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Skin Whitening product

Used in cosmetics and clinics (melasma, freckles, senile lentigines) Hydroquinone (1,4-dihydroxybenzene) Inhibit tyrosinase enzym Inhibit the conversion of DOPA to melanin OTC < 2% Kojic acid, isolated from aspergillus in 1988 Suppress free tyrosinase (chelation of its copper molecule) prevent pigmentation High sensitizing agent Ascorbic acid and its derivatives Reducing o-quinone inactivate tyrosinase Quickly oxidized and decompose in aquose solution not useful as depigmenting agent
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