TY - JOUR
T1 - Hypersensitivity to cell killing and mutation induction by chemical carcinogens in an excision repair-deficient mutant of CHO cells
AU - Thompson, L. H.
AU - Salazar, E. P.
AU - Brookman, K. W.
AU - Hoy, C. A.
PY - 1983
Y1 - 1983
N2 - A strain of Chinese hamster ovary cells that is deficient in nucleotide excision repair, strain UV5, was compared with the normal parental CHO cells in terms of cytotoxicity and mutagenesis after exposure to several chemical carcinogens that are known to produce bulky, covalent adducts in DNA. Induced mutations were measured at the hprt locus using thioguanine resistance and at the aprt locus using azaadenine resistance. The compounds tested that required metabolic activation (using rat or hamster microsomal fractions) were 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, benzo(a)pyrene, aflatoxin B1, 2-acetylaminofluorene, and 2-naphthylamine. The direct-acting compounds (±)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyreneN-acetoxy-2-acetylaminofluorene, and N-OH-2-naphthylamine were also studied. For all compounds except 2-naphthylamine and its active metabolite, the repair-deficient cells were significantly more sensitive to killing than the normal CHO cells. Mutation induction at both loci was also more efficient in UV5 cells in each instance where enhanced cytotoxicity was observed. By using tritium-labeled N-acetoxy-2-acetylaminofluorene, normal and mutant cells.
AB - A strain of Chinese hamster ovary cells that is deficient in nucleotide excision repair, strain UV5, was compared with the normal parental CHO cells in terms of cytotoxicity and mutagenesis after exposure to several chemical carcinogens that are known to produce bulky, covalent adducts in DNA. Induced mutations were measured at the hprt locus using thioguanine resistance and at the aprt locus using azaadenine resistance. The compounds tested that required metabolic activation (using rat or hamster microsomal fractions) were 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, benzo(a)pyrene, aflatoxin B1, 2-acetylaminofluorene, and 2-naphthylamine. The direct-acting compounds (±)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyreneN-acetoxy-2-acetylaminofluorene, and N-OH-2-naphthylamine were also studied. For all compounds except 2-naphthylamine and its active metabolite, the repair-deficient cells were significantly more sensitive to killing than the normal CHO cells. Mutation induction at both loci was also more efficient in UV5 cells in each instance where enhanced cytotoxicity was observed. By using tritium-labeled N-acetoxy-2-acetylaminofluorene, normal and mutant cells.
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U2 - 10.1016/0167-8817(83)90027-5
DO - 10.1016/0167-8817(83)90027-5
M3 - Article
C2 - 6656796
AN - SCOPUS:0021054290
VL - 112
SP - 329
EP - 344
JO - Mutation Research DNA Repair Reports
JF - Mutation Research DNA Repair Reports
SN - 0167-8817
IS - 6
ER -