Genetic regulation of development of thymic lymphomas induced by N-propyl-N-nitrosourea in the rat.
To clarify the linkage between Hbb and Tls-1 (thymic lymphoma susceptible-1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of N-propyl-N-nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6 genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls-1 loci could be demonstrated since WKY rats also developed a high incidence of thymic lymphomas in response to PNU. Nevertheless, thymic lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large tumor growth phenotype, while the [(WKY X BUF) X WKY] backcross generation consisted of rats with either rapidly growing or slowly growing tumors. It was thus concluded that rapid development of thymic lymphomas is determined by a gene, provisionally designated Tls-3. Analysis of the relationship between 6 genetic markers and development of thymic lymphoma in the backcross generation demonstrated that the Tls-3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls-3 may not be identical with Tls-1 and other genes known to be relevant to thymic tumors, but its relationship with Tls-2 remains obscure.
Ogiu
T
T
Division of Biology and Oncology, National Institute of Radiological Sciences, Chiba.
Fukami
H
H
Nishimura
M
M
Matsuyama
M
M
D000818:Animals; D002273:Carcinogens; D003433:Crosses, Genetic; D005260:Female; D005819:Genetic Markers; D008223:Lymphoma / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D008297:Male; D009607:Nitrosourea Compounds; D010641:Phenotype; D051381:Rats; D011915:Rats, Inbred BUF; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013953:Thymus Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology
D002273:Carcinogens; D005819:Genetic Markers; D009607:Nitrosourea Compounds; C020796:propylnitrosourea