Abstract：
:Potassium bromate (KBrO(3)) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO(3) in F344 rats. Detection of cytoplasmic periodic acid-Schiff-positive granules in clear cell tumors, indicative of glycogen accumulation, provides evidence of their biochemical similarity to human counterparts. Mutation in the coding region of the von Hippel-Lindau (VHL) gene is frequently detected in human clear cell renal carcinomas. Detection of VHL mutations in KBrO(3)-induced rat renal tumors could enhance the relevancy of these rat renal tumors for human health risk assessment. Formalin-fixed paraffin-embedded control tissues and renal tumors from male F344 rats exposed to KBrO(3) in the drinking water for 2 years were examined microscopically and were microdissected for DNA extraction. The coding sequence and a promoter region of the VHL gene were examined by polymerase chain reaction-single strand conformation polymorphism and/or DNA sequencing. Two of nine clear cell renal tumors carried the same C to T mutation at the core region of the Sp1 transcription factor binding motif in the VHL promoter and one of four untreated animals had C to T mutation outside the highly conserved core region. Mutation in the VHL coding sequence was only detected in one tumor. No VHL mutations were observed in three chromophilic tumors. KBrO(3)-induced rat renal tumors are morphologically similar to their human counterpart but the genetic basis of tumorigenesis is different.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Shiao YH,Kamata SI,Li LM,Hooth MJ,DeAngelo AB,Anderson LM,Wolf DCdoi
10.1016/s0304-3835(02)00407-xkeywords:
subject
Has Abstractpub_date
2002-12-10 00:00:00pages
207-14issue
1-2eissn
0304-3835issn
1872-7980pii
S030438350200407Xjournal_volume
187pub_type
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