Can a mixed damage interfere with DNA-protein cross-links repair?
Some photochemical and photobiological properties of 4,5',8-trimethylpsoralen (TMP) have been studied in comparison with 1,4,6,8-tetramethyl-2H-furo[2,3-h]quinolin-2 one (FQ) and 8-methoxypsoralen (8-MOP). TMP and FQ can photobind to mammalian cell DNA in vivo, by UVA irradiation, forming DNA-protein cross-links (DPC), but only TMP shows a strong capacity of inducing interstrand cross-links (ISC). The mechanism of DPC formation was studied using the double irradiation method in Chinese hamster ovary (CHO) cells, and DPC were detected by alkaline elution. Both TMP and FQ induce covalent diadducts linking together DNA and proteins. Studying the formation of double strand breaks (DSB) in CHO cells we observed that TMP induced a low amount of DSB, similar to 8-MOP. TMP and 8-MOP induced chromosomal aberrations in CHO cells to the same extent, while FQ appeared to be more active. Our data suggest that the ISC induced by TMP could trap enzymes involved in DPC repair.
Marzano
C
C
Department of Pharmaceutical Sciences of Padova University, Centro di Studio sulla Chimica del Farmaco e dei Prodotti Biologicamente Attivi del C.N.R., Italy. cristina.marzano@unipd.it
Severin
E
E
Bordin
F
F
D000818:Animals; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D019281:Dimerization; D007700:Kinetics; D008730:Methoxsalen / Q000494:pharmacology; D008954:Models, Biological; D008956:Models, Chemical; D017785:Photons; D015363:Quinolones / Q000494:pharmacology; D013938:Thymidine Monophosphate / Q000494:pharmacology; D013997:Time Factors; D014466:Ultraviolet Rays
C101951:1,4,6,8-tetramethyl-2H-furo(2,3-h)quinolin-2-one; D003432:Cross-Linking Reagents; D015363:Quinolones; D013938:Thymidine Monophosphate; D004247:DNA; D008730:Methoxsalen