The Science Behind It All

In the previous blog entitled Sun, Tanning Beds and Malignant Melanoma, Part I – Introduction and Background, the role of the tanning industry in general and the efforts of the Indoor Tanning Association (ITA) specifically in promoting tanning, attempting to deceive the public by making false claims pertaining to the safety and benefits of tanning, proactively attacking and attempting to dispel the overwhelming medical evidence demonstrating the relationship between ultraviolet exposure and skin cancer was highlighted. We also informed the reader of the ITA’s unrelenting campaign to maintain a grip on its tanning clientele by continuing to promulgate misinformation on its website in spite of its acceptance of formal charges brought against it by the Federal Trade Commission in 2010 and demands that its deceitful practices be curtailed. In Part II – The Science Behind It All, we hope not to bore the reader with some – a lot, perhaps – of the details of the scientific evidence backing the American Academy of Dermatology’s and its dermatologist members’ endeavors to educate the American public regarding the dangers of unprotected ultraviolet exposure and tanning.

A brief review of the information previously presented in the blog entitled, Is It Time for Your Total Body Skin Examination? is in order. More than 3.5 million skin cancers are diagnosed in the United States annually, and this number continues to increase at an alarming rate. One in every three cancers diagnosed worldwide is skin cancer, and current estimates indicate that 1 in 5 Americans will develop skin cancer in their lifetime. By the end of this year, it is estimated that there will be 131,810 new cases of melanoma, the deadliest form of skin cancer, 44,250 men and 32,000 women. By 2015, 1 in 50 Americans will develop melanoma in their lifetime. About 75 percent of skin cancer deaths are from melanoma and, on average, one American dies from melanoma every hour. While men over the age of 50 are at a higher risk for developing melanoma, it is the most common form of cancer for young adults 25-29 years old and the second most common form of cancer for adolescents and young adults 15-29 years old.

In July 2009, the International Agency for Research on Cancer (IARC), a working group of the World Health Organization, added ultraviolet radiation (UVR)-emitting tanning devices - tanning beds - to the list of the most dangerous forms of cancer-causing radiation. The interested reader is directed to pages 35 – 90 of the IARC’s most recent monograph on the evaluation of carcinogenic risks to humans entitled RADIATION, Volume 100 D A Review of Human Carcinogens for an informative and thorough exposé regarding the relationship between ultraviolet exposure, both natural and artificial, and skin cancer. There are hundreds of reports substantiating the experimental induction of skin cancers following exposures to UVR in animals. Studies have also demonstrated a number of biochemical mechanisms at work by which UVR, including ultraviolet-A (UVA), ultraviolet-B (UVB) and ultraviolet-C (UVC), induces precancerous and cancerous changes in the skin. Each of these will be presented in limited detail and, hopefully, explained adequately.

Biochemical Reactions – DNA Damage.

UVR has been demonstrated to cause damage to DNA in skin cells. UV-B damages DNA both directly and indirectly, whereas UV-A is poorly absorbed by DNA and, therefore, requires that other factors, primarily photosensitizers, be present to induce indirect modifications of DNA via the generation of so-called photoproducts. As the name implies, photosensitizers sensitize the skin to light, in this case UV-A light radiation. Internal or endogenous (en•dah′•jen•us) photosensitizers include melanin, which is the pigment formed in one’s skin by cells called melanocytes, and proteins containing porphyrins and heme, both of which are building blocks of hemoglobin, the oxygen-carrying component of red blood cells, and flavin groups, which are a group of compounds derived from the B-vitamin (B-2) riboflavin and are essential in the formation of adenosine triphosphate (ATP), the active constituent in energy production for cellular metabolism. External or exogenous (ex•ah′•jen•us) photosensitizers include products that are either applied to the skin, administered orally or by injection, most often as part of a treatment for a medical condition. Examples of these include psoralens (sore′•ah•lěnz), certain antibiotics and immunosuppressant medications. Psoralens are agents which can be applied topically to the skin or taken orally and are administered prior to exposing the skin to UV-A, so-called PUVA therapy, most often employed as a treatment for psoriasis.

Photosensitizing agents are absorbed by UV-A and their molecules become excited, releasing what are called reactive oxygen species - one of the aforementioned photoproducts - i.e. different changes occur in the oxygen molecule which have either a direct or, again, another indirect deleterious effect on DNA. These changes involve electron and energy transfers to the oxygen molecule, the details of which are beyond the realm of this discourse. Additonally, reactive nitrogen species - other photoproducts - such as nitric acid and peroxynitrite, are also formed after photosensitized UV-A exposure and react  with reactive oxygen species to cause, among other detrimental effects, damage to DNA. 

Are you still with me???

These reactive species cause damage to DNA primarily by the formation of cyclobutane–pyrimidine dimers (CPD). Simply stated, pyrimidines are ringed, organic carbon and nitrogen compounds which combine with their purine (slightly more complex, double-ringed carbon and nitrogen compounds) counterparts to form the basic structure of DNA and RNA. UV-B exposure, directly, and UV-A exposure, indirectly, cause 2 pyrimidine molecules, along the assembling spiral, double helix chain of DNA, to form covalent bonds with each other between 4 carbons in a ring (“cyclobutane”), thus interrupting the replication of the DNA chain. Unrepaired dimers are mutagenic, i.e. produce mutations. Pyrimidine dimers are the primary cause of malignant melanomas in human beings. 

Immunosuppression.

UV-R also mediates the conversion of urocanic acid from its natural so-called "trans" chemical configuration in the stratum corneum, the outermost layer of skin where it is predominantly found, to its so-called "cis" configuration.
Among its other potential functions, trans-urocanic acid acts as an endogenous - there's that word again - sunscreen against UV-B – induced DNA damage. Cis-urocanic acid activates white blood cells called suppressor T-lymphocytes, which suppress the immune system from counteracting the untoward effects of UV-B on DNA.

There is a great deal more information regarding the science in support of the cause-and-effect relationship between UV-R exposure and skin cancer. This will be covered in, yet, a third part of this blog entitled, Sun, Tanning Beds and Malignant Melanoma, Part III – More of the Science. We hope to tie things up and complete the blog in Part III. However…as said previously, stay tuned.