Environmental Health Perspectives 105, Supplement 5, September 1997: Article by Unfried et al.

Environmental Health Perspectives 105, Supplement 5, September 1997

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Fiber-specific Molecular Features of Tumors Induced in Rat Peritoneum

Klaus Unfried, ¹ Markus Roller, ² Friedrich Pott, ² Johannes Friemann, ³ and Walter Dehnen ¹

Departments of ¹ Toxicology, ² Experimental Hygiene, ³ Environmental Pathology, Medical Institute of Environmental Hygiene at the Heinrich Heine University Düsseldorf, Düsseldorf, Germany

Abstract
Molecular markers such as mutational spectra or mRNA expression patterns may give some indication of the mechanisms of carcinogenesis induced by fibers and other carcinogens. In our study, tumors were induced by application of crocidolite asbestos or benzo[ a ]pyrene (B[a]P) to rat peritoneum. DNA and RNA of these tumors were subjected to analysis of point mutations and to investigation of mRNA expression patterns. With both assays we found typical features depending on the type of carcinogen applied. The analysis of point mutations in the tumor suppressor gene p53 revealed mutations in the B[a]P-induced tumors. However, in the tumors induced by crocidolite asbestos that were of the same tumor type as those induced by B[a]P, mutations in p53 were not detectable. Every mutation detected on the DNA level causes an amino acid substitution within one of the functional domains of the tumor suppressor protein. Therefore, these mutations seem to be of biological relevance for tumor progression and indicate a difference in the carcinogenesis regarding the type of the carcinogenic substance. An additional specificity of crocidolite-induced tumors was detectable by analyzing the mRNA expression of the tumor suppressor gene WT1 , which is known to be expressed in human mesothelial and mesothelioma cells. A relatively high amount of WT1 mRNA was measured by quantitative competitive reverse transcription-polymerase using RNA extracted from crocidolite-induced tumors. However, WT1 seems to be expressed on a rather low level in tumors induced by B[a]P. -- Environ Health Perspect 105(Suppl 5):1103-1108 (1997)

Key words : asbestos, benzo[a]pyrene, intraperitoneal injection, malignant mesothelioma, p53 , WT1

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 4 June 1997.

The authors thank R. Wirth and W. Brock for their technical assistance.

Address correspondence to Dr. K. Unfried, Medizinisches Institut für Umwelthygiene, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany, Telephone: 0 049 211 3389 361. Fax: 0 049 211 3389 331. E-mail: klaus.unfried@uni-duesseldorf.de

Abbreviations used: B[ a ]P, benzo[ a ]pyrene; CRS, competitive reference standard; DGGE, denaturing gradient gel electrophoresis; HPRT, hypoxanthine phosphoribosyltransferase; PCR, polymerase chain reaction; ROS, reactive oxygen species; RT-PCR, reverse transcription-polymerase chain reaction.

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Last Update: October 28, 1997