Also from this week's C&EN:
Marc Reisch’s cover story reports that the Food & Drug Administration is holding up the approval of eight new sun-filtering molecules currently used in European sunscreens. Reisch quotes a representative of the sunscreen lobby (Public Access to SunScreens coalition, or PASS) as saying: “ ‘Of course we have to be safe.’ … But PASS, he notes, is also concerned about increasing cancer rates. The group argues that the eight pending [molecules] are important tools for preventing skin cancer.”
The article continues: “Melanoma rates skyrocketed 200% between 1973 and 2011.”
What the PASS lobbyist forgot to mention was that during this period sunscreen use also skyrocketed. In fact, just in the past decade (2001–10), the incidence of melanoma increased by 1.5% (www.cdc.gov/cancer/skin/statistics) while the use of sunscreen remained stable (National Cancer Institute, “Cancer Trends Progress Report”).
Although sunscreen clearly protects against sunburn—the redness, swelling, and pain due to inflammation—it is not at all clear that it also protects against skin cancer. In fact, in what has been dubbed the “sunscreen-melanoma controversy,” a number of recent studies have reported either an increase in skin cancer incidence with increased sunscreen use or else no correlation between the two.
Two current hypotheses attempt to explain this surprising disconnect. Thomas M. Chiang and others implicate the inhibition of nitric oxide synthase by sunscreens (Melanoma Res.2005, 15, 3). It has also been known for decades that the inorganic titanium and zinc oxides commonly found in sunscreens have a dual effect: Not only do these crystals filter UV-A and UV-B light, they also catalyze the photogeneration of reactive oxygen species (ROS), for example, superoxide and hydroxyl radicals. These ROS can then oxidize DNA and trigger mutations that lead to cancer.
The bottom line is that although it makes sense to apply sunscreen as a protection against sunburn, one should not assume that this also protects against the later development of skin cancer. The latter correlation has not yet been proven, and some literature even suggests the opposite.
Todd P. SilversteinMy question is this - how do ROS get past the epidermis?
Salem, Ore.
Also, this is a problem that I have with scientific discussions in the letters to the editor at C&EN; how are we supposed to evaluate these claims? (not that I am more or less skeptical of these claims, as opposed to any other claims.)
My understanding is that melanoma link is certainly a good guess (given what we can see with skin aging) and demonstrated: http://jco.ascopubs.org/content/29/3/257.full
ReplyDeleteSomeone's RO1 Specific Aims page? Maybe if he publicizes the idea it'll get some traction in the next study section?
ReplyDeleteEither way, as you say how do we evaluate such claims? it's like commenting at a blog when the next comment can't come in for a month. Archaic at best.
"Also, this is a problem that I have with scientific discussions in the letters to the editor at C&EN; how are we supposed to evaluate these claims?"
ReplyDeleteAs opposed to the Editor's page?
Primary ROS generate longer lived, less reactive (but still damaging!) secondary species. The canonical example is peroxide, which easily diffuses through tissue.
ReplyDeleteThanks, a.e.! That's quite on point.
DeleteIt's also a bit of a cascade effect from a system viewpoint, which we're starting to glimpse from the perspective of studying the oxidative potential of ambient particular pollution.
Delete"My question is this - how do ROS get past the epidermis?"
ReplyDeleteThe very quick and dirty response is that ROS are generally present throughout many living organisms. They're generated intracellularly through metabolism processes and have multiple roles including cell signaling in immune responses, homeostasis, and apoptosis - in other words ROS play multiple crucial roles in regulating biological systems. So the question as put doesn't make much sense - the ROS are already present - this is undergrad biochemistry.
In the case of exogenously stimulated ROS, it seems that the UV radiation promotes radiolysis. The resulting (excessive) ROS then drive lipid, protein and DNA damage yielding carcinogenesis. The cancer cells are dependent on ROS for progression and metabolism processes - ROS also activate transcription factors yielding expression of proteins that both enhance tumor cell survival and proliferation and suppress tumor cells. The basis for most cancer treatment is in stimulating excessive production of ROS to induce cancer cell suppression and apoptosis. The pathways through which these actions occur are complex and numerous enough to defy quick explanation or even just enumeration, but this gives a rough idea idea as to the dual nature of ROS in regulating cancer cells.
Maybe I've misunderstood the issue?
DeleteI think the question is, how do the ROS make it past the dead epidermis into the living cells beneath.
DeleteBoth UVA and UVB penetrate beyond the epidermis. UVB penetrates into the dermis and UVA penetrates into subcutaneous tissue.
DeleteThe ROS are already being produced in these layers, but the UV radiation promotes more of it.
Again, I really don't understand how the question as put makes any sense - the ROS are already past the epidermis and functioning in their multiple roles as existing parts of the system - they aren't external to it. The UV radiation promotes increased generation of ROS in layers below the epidermis.
I can't speak for Squib, but this is my question. According to this, the formula is:
DeleteUV + TiO2 crystals = ROS
I don't think anyone is disputing this.
But if the TiO2 crystals (as part of the suncreen) are only at the level of the epidermis, then the ROS must travel.
If the TiO2 crystals go past the epidermis, then OK, I can see TiO2 having an effect.
This formulation of the question makes a little more sense.
DeleteHowever, "According to this, the formula is: UV + TiO2 crystals = ROS" is clearly according to neither of these hypotheses unless you're just talking about superoxide anion radicals and singlet oxygen alone. If you included water in that, then maybe you'd have something.
Also, I'd take issue with the claim that "the ROS must travel" given that UVA and UVB affect ROS production at dermal and subdermal layers. It seems to me that all TiO2 has to do is promote ROS production in these layers, or enhance the promotion of ROS production in these layers, directly or indirectly, to induce carcinogenesis.
However, if you think that "the ROS must travel" through or past the corneocytes of the stratum corneum, there are two ways in which this might occur: 1) via "transport along sweat pores, hair follicles, and skin (sebaceous) glands" and 2) via paracellular routes where "transport of substances may be facilitated by liquid domains created by the unsaturated moieties of the ceramides." Apparently also disruption of the (stratum corneum) skin barrier may be caused by UVB, leading to "an increased epidermal permeability that is possibly associated to defective lipid lamellar layers in the stratum corneum" - alterations in the integrity of which can result from daily sun exposure - leading to greater penetration of particles.
There is an interesting and relevant discussion here (from which some of the quotes above are taken):
Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781714/
I'd be interested to also know the rates of tanning bed use over the same period.
ReplyDelete