TY - JOUR
T1 - (6-4) Photoproducts and not cyclobutane pyrimidine dimers are the main UV-induced mutagenic lesions in Chinese hamster cells
AU - Zdzienicka, Małgorzata Z.
AU - Venema, Jaap
AU - Mitchell, David L.
AU - van Hoffen, Anneke
AU - van Zeeland, Albert A.
AU - Vrieling, Harry
AU - Mullenders, Leon H.F.
AU - Lohman, Paul H.M.
AU - Simons, Jo W.I.M.
N1 - Funding Information:
We thank I. Neuteboom, S. Stuivenberg and A.R. Filon for skillful technical assistance. This work w~s supported by the contract with the European Community, with the University of Leiden (Euratom, Contract No. BI6-E-166 NL), by Grant IKW 90-03 from the Dutch Cancer Society and by the Netherlands Foundation for Scientific Research (Grant No. 900-501-074).
PY - 1992/1
Y1 - 1992/1
N2 - A partial revertant (RH1-26) of the UV-sensitive Chinese hamster V79 cell mutant V-H1 (complementation group 2) was isolated and characterized. It was used to analyze the mutagenic potency of the 2 major UV-induced lesions, cyclobutane pyrimidine dimers and (6-4) photoproducts. Both V-H1 and RH1-26 did not repair pyrimidine dimers measured in the genome overall as well as in the active hprt gene. Repair of (6-4) photoproducts from the genome overall was slower in V-H1 than in wild-type V79 cells, but was restored to normal in RH1-26. Although V-H1 cells have a 7-fold enhanced mutagenicity, RH1-26 cells, despite the absence of pyrimidine dimer repair, have a slightly lower level of UV-induced mutagenesis than observed in wild-type V79 cells. The molecular nature of hprt mutations and the DNA-strand specificity were similar in V79 and RH1-26 cells but different from that of V-H1 cells. Since in RH1-26 as well as in V79 cells most hprt mutations were induced by lesions in the non-transcribed DNA strand, in contrast to the transcribed DNA strand in V-H1, the observed mutation-strand bias suggests that normally (6-4) photoproducts are preferentially repaired in the transcribed DNA strand. The dramatic influence of the impaired (6-4) photoproduct repair in V-H1 on UV-induced mutability and the molecular nature of hprt mutations indicate that the (6-4) photoproduct is the main UV-induced mutagenic lesion.
AB - A partial revertant (RH1-26) of the UV-sensitive Chinese hamster V79 cell mutant V-H1 (complementation group 2) was isolated and characterized. It was used to analyze the mutagenic potency of the 2 major UV-induced lesions, cyclobutane pyrimidine dimers and (6-4) photoproducts. Both V-H1 and RH1-26 did not repair pyrimidine dimers measured in the genome overall as well as in the active hprt gene. Repair of (6-4) photoproducts from the genome overall was slower in V-H1 than in wild-type V79 cells, but was restored to normal in RH1-26. Although V-H1 cells have a 7-fold enhanced mutagenicity, RH1-26 cells, despite the absence of pyrimidine dimer repair, have a slightly lower level of UV-induced mutagenesis than observed in wild-type V79 cells. The molecular nature of hprt mutations and the DNA-strand specificity were similar in V79 and RH1-26 cells but different from that of V-H1 cells. Since in RH1-26 as well as in V79 cells most hprt mutations were induced by lesions in the non-transcribed DNA strand, in contrast to the transcribed DNA strand in V-H1, the observed mutation-strand bias suggests that normally (6-4) photoproducts are preferentially repaired in the transcribed DNA strand. The dramatic influence of the impaired (6-4) photoproduct repair in V-H1 on UV-induced mutability and the molecular nature of hprt mutations indicate that the (6-4) photoproduct is the main UV-induced mutagenic lesion.
KW - (6-4) Photoproducts
KW - Pyrimidine dimers
KW - UV-induced mutagenesis
UR - https://www.scopus.com/pages/publications/0026800456
UR - https://www.scopus.com/pages/publications/0026800456#tab=citedBy
U2 - 10.1016/0921-8777(92)90051-4
DO - 10.1016/0921-8777(92)90051-4
M3 - Article
C2 - 1376437
AN - SCOPUS:0026800456
SN - 0921-8777
VL - 273
SP - 73
EP - 83
JO - Mutation Research-DNA Repair
JF - Mutation Research-DNA Repair
IS - 1
ER -