Mutations in DNA polymerase beta mRNA of stilbene estrogen-induced kidney tumors in Syrian hamster.
We report here the alteration(s) in the expression of the DNA repair gene, DNA polymerase beta, in kidney tumors induced by stilbene estrogen (diethylstilbestrol, DES). RT-PCR, slot blotting, and Northern blotting experiments revealed that expression of DNA polymerase beta (DNA pol beta) was several fold lower in stilbene-estrogen-induced kidney tumors than in age-matched controls. Several mutations were identified in DNA pol beta mRNA from DES-induced kidney tumors, but not in age-matched control kidney. The mutations in DNA pol beta mainly occurred in the catalytic domain of pol beta, and not in the DNA binding domain. All the mutations produced a stop codon at nucleotide 199 indicating that a protein of aberrant size may be synthesized. These data suggest that mutation of DNA pol beta coupled with attenuation in expression might compromise the DNA repair system. This in turn may allow a greater error rate during DNA repair and the accumulation of lesions in the genome.
Yan
Z J
ZJ
Department of Environmental Health Sciences, University of Alabama, Birmingham 35294, USA.
Roy
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D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D006224:Cricetinae; D004256:DNA Polymerase I / Q000235:genetics*; D004054:Diethylstilbestrol; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics*; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger
D012333:RNA, Messenger; D004054:Diethylstilbestrol; D004256:DNA Polymerase I