Mutagenesis vol. 19 no. 1 pp. 67-73,
January 2004
© 2004 UK Environmental Mutagen Society/Oxford University Press
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
Department of Environmental Health Sciences, University of Alabama at Birmingham, 1665 University Boulevard, 530 Ryals Building, Birmingham, AL 35294-0022, USA and 1Department of Pathology, University of Valencia, Valencia 17-46010, Spain
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.
2To whom correspondence should be addressed. Tel: +1 205 934 6081; Fax: +1 205 975 6341; Email: Royd{at}uab.edu
Received on August 18, 2003; revised on October 27, 2003; accepted on October 30, 2003