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Burke. Plast Aesthet Res 2020;7:59 I http://dx.doi.org/10.20517/2347-9264.2020.154 Page 5 of 16

Figure 2. Squamous cell carcinoma multiplicity (number of tumors/mouse) in Skh:1 female mice after topical application of BaP (8
2
nmol) followed by exposure to ultraviolet A (UVA) (40 kg/m ) three times weekly for 25 weeks. For 5 weeks after treatments were
[1]
discontinued, tumors were still counted (Wang et al. ). (Printed with consent of the authors.). BaP: benzo[a]pyrene
[13]
mitochondrial superoxide anion production . In human fibroblasts in vitro, IR-A induces genes regulating
[14]
apoptosis, extracellular matrix, calcium regulation, and other signaling . Solar elastosis is markedly
exacerbated by IR-A in two ways: (1) stimulation of MMP-12 which specifically degrades elastin; and
[13]
(2) abnormal production of the major components of elastin-fibrillin-1,2 and tropoelastin . Along with
degradation of collagen, this accumulation of abnormal, clumped elastin in the dermis is the paramount
cause of the crepe-like, saggy, wrinkled appearance of photoaged skin.

SYNERGY: UVA AND POLLUTANTS
Atmospheric pollutants fill the air in modern cities. Outside, traffic exhausts, power plants and factories
pollute, and, inside, stoves, heaters, fireplaces, candles, and cigarette smoke. Organic and inorganic
compounds are emitted. PAHs are ubiquitous in our air, water, and food. The most significant PAH in
urban environments is benzo[a]pyrene (BaP). These PAHs are absorbed onto and within the larger PM
pollutants. When inhaled or absorbed after direct contact with mucosa or skin, these PAHs are metabolized
to quinones which generate ROS.

Today, the levels of PAHs are lower than those of 40-50 years ago, well below a toxic or carcinogenic level.
However, with simultaneous exposure of the skin to PAHs and UVA radiation, synergistic interactions
increase oxidative damage, leading to increased extrinsic damage to the skin with resultant photoaging and
skin cancer.

In mouse model experiments, exposure to low doses of BaP alone, or to UVA alone, does not initiate skin
cancer. However, exposure to 1.8% of the carcinogenic dose of BαP with simultaneous exposure to 12.5% of
the carcinogenic dose of UVA could initiate skin cancer [1,15] , as shown in Figure 2 (this exposure to UVA is
comparable to 2 h of midday sunlight on a summer day in New York City).

Synergistic damage was further demonstrated in vitro. High concentrations of d-OHdG and hydrogen
peroxide (H O ) were generated when calf-thymus DNA was exposed to UVA after incubation with BaP;
2
2