Mechanisms of mutation formation with long‐wave ultraviolet light (UVA)

Abstract

Long-wave ultraviolet (UV) A light is able to damage DNA, to cause mutations, and to induce skin cancer, but the exact mechanisms of UVA-induced mutation formation remain a matter of debate. While pyrimidine dimers are well established to mediate mutation formation with shortwave UVB, other types of DNA damage, such as oxidative base damage, have long been thought to be the premutagenic lesions for UVA mutagenesis. However, pyrimidine dimers can also be generated by UVA, and there are several lines of evidence that these are the most important premutagenic lesions not only for UVB- but also for UVA-induced mutation formation. C-->T transition mutations, which are generated by pyrimidine dimers, are called UV-signature mutations. They cannot be interpreted to be solely UVB-induced, as they are induced by UVA as well. Furthermore, there is no consistent evidence for a separate UVA-signature mutation that is only generated with UVA. We hypothesize that a weaker anti-mutagenic cellular response, but not a different type of DNA damage, may be responsible for a higher mutation rate per DNA photoproduct with UVA, as compared with UVB.

Effects of UV wavelength on cell damages caused by UV irradiation in PC12 cells

“…UV light is absorbed by tryptophan and tyrosine in proteins at 310 nm and 290 nm, respectively [42,43]. The most effective wavelength, within the UVB range, for inducing DNA photoproducts in the basal layer of the epidermis is 300 nm [41]. The relationship between CPD formation and the irradiation dose was consistent with our expectation: the magnitude of CPD formation increased in a dose-dependent manner.…”

“…DNA and proteins absorb is maximally at 260 nm and 280 nm, respectively [8,41]. UV light is absorbed by tryptophan and tyrosine in proteins at 310 nm and 290 nm, respectively [42,43].…”

Ultraviolet Light as a Modulator of Melanoma Development

“…UVA-specific lesions in the p53 gene have been detected in skin constructs and squamous tumours (Agar et al, 2004;Huang et al, 2009). In contrast, in vivo studies using "Big Blue" mice, and in vitro data, suggests that UVA-induced mutations are mainly of the pyrimidine dimer type (Mouret et al, 2006;Besaratinia & Pfeifer, 2008;Runger & Kappes, 2008). An interesting idea regarding the role of UVA in melanoma is that UVA and UVB generate a similar DNA mutation spectrum (although UVA is much less effective at inducing CPDs), but that UVA-induced cellular stress and repair response is not as great, thus lesions may not be as effectively removed (Runger & Kappes, 2008).…”

“…In contrast to UVB, UVA is generally extremely inefficient at inducing CPDs, oxidative damage, erythema, and non-melanoma skin cancer in mice (De Gruijl et al, 1993;Besaratinia & Pfeifer, 2008;Runger & Kappes, 2008). However UVA can induce 8-oxoguanine (8-oxoG) oxidative adducts that can results in the formation of G-T transversions (Agar et al, 2004).…”

Effect ofTinospora cordifoliaon the reduction of ultraviolet radiation‐induced cytotoxicity and DNA damage in PC12 cells

“…[12] Most of the mutagenic and carcinogenic effects of UV radiation have long been attributed to the shorter wavelengths of UVB and UVC. [13] Many plant products rich in bioactive molecules capable of protecting DNA from radiation-induced damage have been investigated. [14] Identification and development of safe, non-toxic, and effective radioprotective compounds are of enormous importance in mitigating the toxic effect of UV radiation-induced DNA damage.…”