Mesotheliomas induced in rats by the fibrous mineral erionite are independent from p53 alterations.
The development of human malignant mesothelioma (MM) is strongly associated with occupational or environmental exposure to certain natural mineral fibers, although the genetic mechanisms underlying this malignancy remain unclear. Although the p53 gene is frequently mutated in various tumors, human asbestos-associated MMs appear to develop independently from p53 alterations. The high mesotheliomagenic potency of natural fibrous mineral erionite is well established in humans and rodents, but no data regarding genetic alterations in erionite-associated tumors are currently available. Previous speculations that the oncogenic mechanisms underlying asbestos and erionite carcinogenesis may differ led us to examine whether the p53 gene is targeted in erionite carcinogenesis. Fifteen erionite-induced rat MMs as well as six cell lines derived from asbestos-induced and spontaneous rat MM were analyzed for p53 mutations by direct DNA sequencing and immunohistochemical analysis. Both approaches did not reveal p53 alterations in rat MM samples used in the study indicating that, similar to asbestos carcinogenesis, erionite carcinogenesis does not target the p53 tumor suppressor gene.
Kleymenova
E V
EV
Chemical Industry Institute of Toxicology, Research Triangle Park, NC, USA. sa83514@odin.mdacc.tmc.edu
Horesovsky
G
G
Pylev
L N
LN
Everitt
J
J
D000818:Animals; D015197:Carcinogenicity Tests; D004252:DNA Mutational Analysis; D007150:Immunohistochemistry; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D017641:Zeolites
D016159:Tumor Suppressor Protein p53; C083174:erionite; D017641:Zeolites; D012313:RNA