Age, sex and co-exposure to N-ethyl-N-nitrosourea influence mutations in the Alu repeat sequences in diethylstilbestrol-induced kidney tumors in Syrian hamsters.
We report, for the first time, mutations in the Alu repeat regions in the genome of kidney tumors induced by diethylstilbestrol in Syrian hamsters. Among the 66 loci amplified by 11 random primers, 28 loci exhibited insertions, deletions or losses or gains in intensity in the genome of kidney tumor tissues compared with normal kidney tissues from age-matched hamsters. Higher numbers of mutated Alu loci were observed in the tumors of old hamsters compared with young hamsters. In N-ethyl-N-nitrosourea- and diethylstilbestrol-treated hamsters deletion of a 0.59 kb locus amplified with primer OPC03 was observed in most of the female hamsters, but not in male hamsters. An insertion mutation of a 0.498 kb locus amplified with primer OPC03 was observed in 12 of 36 diethylstilbestrol-induced kidney tumors. The cloning and sequencing of the 0.498 kb locus amplified with primer OPC03 revealed that it had significant sequence similarity to the mouse RIKEN cDNA clone. These findings indicate that age, sex and co-exposure to N-ethyl-N-nitrosourea influence mutations in the Alu repeat sequences in the genome of diethylstilbestrol-induced kidney tumors in Syrian hamsters. Structural alterations in Alu repeats in critical target genes may be involved in diethylstilbestrol-induced carcinogenesis.
Singh
Kamaleshwar P
KP
Department of Environmental Health Sciences, University of Alabama at Birmingham, 1665 University Boulevard, 530 Ryals Building, Birmingham, AL 35294-0022, USA.
Lopez-Guerrero
Jose Antonio
JA
Llombart-Bosch
Antonio
A
Roy
Deodutta
D
D000367:Age Factors; D020087:Alu Elements; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity; D006224:Cricetinae; D017931:DNA Primers; D004054:Diethylstilbestrol / Q000633:toxicity*; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000235:genetics; D019105:Random Amplified Polymorphic DNA Technique; D012689:Sequence Homology, Nucleic Acid; D012737:Sex Factors; D014157:Transcription Factors / Q000235:genetics
D002273:Carcinogens; D017931:DNA Primers; D011506:Proteins; C443111:Spacdr protein, mouse; D014157:Transcription Factors; D004054:Diethylstilbestrol; D005038:Ethylnitrosourea