K-ras mutations in (PuO2)-Pu-239 canine lung neoplasms

Single-strand conformational polymorphism (SSCP) analysis and direct sequen cing methods were used to examine lung tumors derived from a cohort of beag le dogs with inhalational exposures to (PuO2)-Pu-239. These exposures were done at Pacific Northwest Laboratories where 18-month-old beagle dogs were given (PuO2)-Pu-239 by single-dose inhalation and allowed to live out their Life-spans. Formalin-fixed paraffin-embedded blocks of tissues from 25 dog s exposed to (PuO2)-Pu-239 by aerosol inhalation which later developed lung tumors were available for this study. Two of 25 tumors had mutations withi n exon 1 of K-ras detected by SSCP analysis. Both mutations were GGT to GAT transitions at codon 12 confirmed by direct sequencing experiments. One wa s an adenocarcinoma from the medium-high exposure group and the other was a broncheolo-alveolar carcinoma from the medium-low exposure group. The rate of K-ras mutations in plutonium-induced lung tumors described herein (8%) was greater than previously described in canine plutonium-induced lung tumo rs (0%), but was less than that which we have described in spontaneous cani ne lung cancer (16%), less than that reported for human spontaneous non-sma ll cell lung cancer (13-36%) and less than that described in rats with spon taneous lung cancer (40%) or lung tumors following Pu-239 inhalation exposu re (46%). (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.