Ablation of T cell immunity differentially influences tumor risk in inbred BD rat strains.

Inbred rat strains BDIX and BDIV are constitutionally susceptible and resistant, respectively, to the development of malignant peripheral nerve sheath tumors (MPNST) induced by neonatal exposure to N-ethyl-N-nitrosourea (EtNU). They represent a model system for analysis of molecular and cellular processes underlying differential cancer susceptibility. A point mutation in the Neu/ErbB-2 gene is an early marker of Schwann precursor cells at high risk of malignant conversion and is diagnostic of the resulting MPNST predominantly developing in the trigeminal nerves.

The interaction mode of premalignant Schwann and immune effector cells during chemically induced carcinogenesis in the rat peripheral nervous system is strongly influenced by genetic background.

Contrary to rats of the highly sensitive inbred strain BDIX, BDIV rats are resistant to the induction of malignant schwannomas by N-ethyl-N-nitrosourea, arising predominantly in the trigeminal nerves. A point mutation of the neu/erbB-2 gene diagnostic of N-ethyl-N-nitrosourea-induced rat schwannomas is an early marker of Schwann precursor cells at high risk of subsequent malignant transformation. Neu-mutant cells initially arise at a similar frequency in sensitive and resistant animals.

Gender-specific polygenic control of ethylnitrosourea-induced oncogenesis in the rat peripheral nervous system.

The inbred BD rat strains constitute a model system for analysis of the genetic basis of susceptibility or resistance to the development of neural tumors, as they exhibit distinct strain-specific differences regarding the sensitivity to tumor induction by the alkylating carcinogen N-ethyl-N-nitrosourea (EtNU). Among the different BD strains, BDIX and BDIV rats, respectively, are either highly susceptible or entirely resistant to the development of EtNU-induced malignant schwannomas of the peripheral nervous system (PNS), predominantly of the trigeminal nerves. We have previously mapped one locus associated with susceptibility/resistance to schwannoma induction to the telomeric third of chromosome 10 (Mss1) in segregating (BDIX x BDIV) crosses.

A 6-Mb contig-based comparative gene and linkage map of the rat schwannoma tumor suppressor region at 10q32.3.

Frequent genetic aberrations of malignant schwannomas induced by the alkylating agent N-ethyl-N-nitrosourea in hybrids from inbred BD rat strains include allelic imbalances of the telomeric 20 Mb of chromosome 5 (Dis-2) and of the telomeric 5 Mb of chromosome 10q32 (Dis-1) in 59 and 94% of the tumors, respectively. The Dis-1 minimal loss of heterozygosity consensus region extends from D10Rat4 to the telomere and harbors a putative tumor suppressor gene(s). We constructed a 6-Mb BAC/PAC contig containing more than 70 known genes, 18 mapped microsatellites, and further ESTs/reference RNAs.

Ninth Japanese-German Workshop on Molecular and Cellular Aspects of Carcinogenesis, Essen, Germany, 18-20 September, 2003.

The Japanese-German Workshops "Molecular and Cellular Aspects of Carcinogenesis," held biennially since 1987, have been organized traditionally at the University of Essen Medical School and West German Cancer Center Essen in Germany. This 9th Workshop was held on September 18-20, 2003. It was generously supported by the Cancer Research Program of the Ministry of Education, Culture, Sports, Science and Technology and the International Cooperation Program for the 2nd Term Comprehensive 10-Year Strategy for Cancer Control of the Ministry of Health, Labour and Welfare on the Japanese side, and by the Deutsche Forschungsgemeinschaft (DFG) on the German side.

Loss of heterozygosity in malignant rat schwannomas chemically induced in hybrids of inbred rat strains with differential tumor susceptibility.

Rats of the inbred BD strains strongly differ in their susceptibility to the induction of tumors of the central (CNS) and peripheral nervous system (PNS) by N-ethyl-N-nitrosourea (EtNU). Malignant schwannomas induced in (BDIX x BDIV) and (BDIX x BDVI) rat hybrids were analyzed to identify genetic alterations associated with EtNU-induced tumorigenesis in the PNS. EtNU-induced schwannomas exclusively exhibit an A:T T:A transversion mutation of the neu/Erbb-2 gene located on chromosome 10, with subsequent loss of the wild-type neu/Erbb-2 allele at a post-initiation stage.