title: Wavelength dependence of ultraviolet radiation-induced DNA damage as determined by laser irradiation suggests that cyclobutane pyrimidine dimers are the principal DNA lesions produced by terrestrial sunlight.
abstract: To elucidate the involvement of specific ultraviolet (UV) wavelengths in solar mutagenesis, we used a laser system to investigate the induction of DNA damage, both in the overall genome and at the nucleotide resolution level, in the genomic DNA of transgenic Big Blue mouse fibroblasts irradiated with a series of UV wavelengths, inclusive of UVC (λ<280 nm), UVB (λ=280-320 nm), and UVA (λ>320 nm). Subsequently, we sought correlation between the locations of UV-induced DNA lesions in the cII transgene of irradiated DNA samples and the frequency distribution and codon position of the induced cII mutations in counterpart mouse cells irradiated with simulated sunlight. Using a combination of enzymatic digestion assays coupled with gel electrophoresis, immunodot blot assays, and DNA footprinting assays, we demonstrated a unique wavelength-dependent formation of photodimeric lesions, i.e., cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts [(6-4)PPs], based on direct UV absorption of DNA, in irradiated mouse genomic DNA, which could partially explain the induction of mutations in mouse cells irradiated with simulated sunlight. Most notably, there was a divergence of CPD and (6-4)PP formation at an irradiation wavelength of 296 nm in mouse genomic DNA. Whereas substantial formation of (6-4)PPs was detectable in samples irradiated at this wavelength, which intensified as the irradiation wavelength decreased, only small quantities of these lesions were found in samples irradiated at wavelengths of 300-305 nm, with no detectable level of (6-4)PPs in samples irradiated with longer wavelengths. Although CPD formation followed the same pattern of increase with decreasing wavelengths of irradiation, there were substantial levels of CPDs in samples irradiated with UVB wavelengths borderlined with UVA, and small but detectable levels of these lesions in samples irradiated with longer wavelengths. Because the terrestrial sunlight spectrum rolls off sharply at wavelengths ~300 nm, our findings suggest that CPDs are the principal lesion responsible for most DNA damage-dependent biological effects of sunlight.
authors: Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. ania@coh.org
authors: Ahmad
authors: A
authors: Besaratinia
authors: Jae-In
authors: JI
authors: Yoon
authors: Christi
authors: C
authors: Schroeder
authors: Stephen E
authors: SE
authors: Bradforth
authors: Myles
authors: M
authors: Cockburn
authors: Gerd P
authors: GP
authors: Pfeifer
references: Curr Oncol Rep. 2010 Sep;12(5):319-26
references: 20623386
references: J Biol Chem. 2001 Nov 30;276(48):44688-94
references: 11572873
references: Mol Cell Biol. 1995 Aug;15(8):4572-7
references: 7623848
references: Biophys J. 2009 Feb;96(3):1151-8
references: 19186150
references: J Biol Chem. 2000 Sep 1;275(35):26732-42
references: 10827179
references: Mutat Res. 2009 Apr 26;663(1-2):7-14
references: 19150617
references: Photodermatol Photoimmunol Photomed. 2008 Feb;24(1):2-10
references: 18201350
references: Photochem Photobiol. 1987 Jun;45(6):775-80
references: 3628500
references: J Chem Phys. 2006 Jul 28;125(4):44515
references: 16942164
references: J Pharm Pharmacol. 2008 Aug;60(8):969-76
references: 18644190
references: Skin Pharmacol Appl Skin Physiol. 2002 Sep-Oct;15(5):316-20
references: 12239425
references: J Phys Chem B. 2011 Mar 3;115(8):1889-94
references: 21294562
references: J Epidemiol. 1999 Dec;9(6 Suppl):S102-14
references: 10709358
references: Appl Theor Electrophor. 1988;1(1):11-8
references: 3154955
references: Photochem Photobiol. 1991 Aug;54(2):225-32
references: 1780359
references: Nucleic Acids Res. 1992 Jan 25;20(2):225-9
references: 1311069
references: Radiat Res. 2005 Oct;164(4 Pt 1):440-5
references: 16187746
references: FASEB J. 2008 Jul;22(7):2379-92
references: 18326785
references: J Am Chem Soc. 2009 May 13;131(18):6460-7
references: 19374336
references: Methods. 2009 May;48(1):35-9
references: 19245834
references: Photochem Photobiol. 1997 Mar;65(3):543-9
references: 9077139
references: Biochemistry. 1998 Aug 18;37(33):11599-604
references: 9708997
references: Mutagenesis. 2003 Nov;18(6):511-9
references: 14614186
references: Photochem Photobiol. 2006 Sep-Oct;82(5):1219-25
references: 16808595
references: Nucleic Acids Res. 1998 Apr 1;26(7):1807-11
references: 9512556
references: Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10058-63
references: 16009942
references: Photochem Photobiol. 1990 Oct;52(4):819-23
references: 2089431
references: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13538-43
references: 16157879
references: Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4954-9
references: 15041750
references: EMBO J. 1995 May 15;14(10):2393-9
references: 7774597
references: Radiat Res. 1981 Jun;86(3):399-409
references: 6264537
references: Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2350-4
references: 7892270
references: Photochem Photobiol. 1991 Nov;54(5):741-6
references: 1665910
references: J Mol Biol. 2000 Jun 9;299(3):681-93
references: 10835277
references: Photochem Photobiol. 1993 Jan;57(1):163-74
references: 8389052
references: Photochem Photobiol Sci. 2009 Jul;8(7):903-11
references: 19582264
references: Methods. 2002 Sep;28(1):4-13
references: 12231182
references: Mutat Res. 2005 Apr 1;571(1-2):3-17
references: 15748634
references: Proc Natl Acad Sci U S A. 1974 Sep;71(9):3363-6
references: 4530308
references: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7219-24
references: 12775760
references: Sci STKE. 2001 Apr 10;2001(77):pl1
references: 11752648
references: Br J Dermatol. 2002 Apr;146 Suppl 61:1-6
references: 11966724
references: Gastroenterology. 2009 Sep;137(3):1127-37, 1137.e1-5
references: 19524575
references: J Mol Biol. 1998 Nov 27;284(2):297-311
references: 9813119
references: Carcinogenesis. 1994 Feb;15(2):297-300
references: 8313521
references: DNA Repair (Amst). 2006 Nov 8;5(11):1373-83
references: 16876489
references: J Mol Biol. 1966 May;17(1):237-54
references: 4289765
references: EMBO J. 1987 Oct;6(10):3177-83
references: 3319582
references: Mutat Res. 2005 Apr 1;571(1-2):19-31
references: 15748635
references: DNA Repair (Amst). 2005 Jul 12;4(7):836-44
references: 15950551
references: J Invest Dermatol. 2006 Mar;126(3):667-75
references: 16374481
references: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13765-70
references: 16954188
references: Methods Enzymol. 2000;319:290-6
references: 10907520
references: Cancer Res. 1993 Jan 1;53(1):53-60
references: 8416751
references: Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):176-80
references: 8552599
references: J Phys Chem B. 2006 Jun 15;110(23):11037-9
references: 16771360
references: Carcinogenesis. 2006 Aug;27(8):1526-37
references: 16344267
references: Photochem Photobiol. 1987 Jun;45(6):781-6
references: 3628501
references: Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9073-8
references: 8799156
references: Methods Enzymol. 1999;304:548-71
references: 10372381
references: J Photochem Photobiol B. 1999 Mar;49(1):71-80
references: 10365447
references: Mutat Res. 2004 Nov 22;556(1-2):135-42
references: 15491641
references: Annu Rev Biochem. 2004;73:39-85
references: 15189136
references: Exp Dermatol. 2010 Feb;19(2):81-8
references: 20067521
references: Photochem Photobiol. 1990 Feb;51(2):161-7
references: 2333334
references: Cancer Lett. 2008 Aug 18;267(1):18-25
references: 18406515
references: Br J Dermatol. 1999 Jun;140(6):1023-30
references: 10354066