title: Hematopoietic proliferative lesions in the spleen of rasH2 transgenic mice treated with MNU.
abstract: In this study, rasH2-Tg mice treated with N-methyl-N-nitrosurea (MNU) developed exuberant hematoproliferative changes in the spleen that included dysplasia and features of neoplasia. Hematoproliferative change was characterized as exuberant proliferation of hematopoietic cells within the spleen that distorted but did not displace normal splenic morphologic features. The hematopoietic cells were of mixed lineage, but one type, often erythroid, predominated. Cellular atypia was present in all mice with hematoproliferative change, and dysplasia was present in five of eight examined. Hematoproliferative neoplasia was characterized by similar cytologic features but also resulted in displacement/disruption of normal splenic architecture and increased numbers of unidentified blast cells. One case was differentiated toward myeloid proliferation, suggesting granulocytic leukemia. Affected mice had other neoplasms, such as lymphoma and anemia. These proliferative and dysplastic lesions of the spleen in rasH2-Tg mice treated with MNU require additional characterization to definitively differentiate them from the reactive hematopoiesis that can occur in response to inflammatory, neoplastic, or hematopoietic insults in mice.
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana 46140, USA. longgg@sbcglobal.net
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Long
authors.forename: Dawn G
authors.initials: DG
authors.lastname: Goodman
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Credille
authors.forename: Peter C
authors.initials: PC
authors.lastname: Mann
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wilson
authors.forename: Richard
authors.initials: R
authors.lastname: Cardy
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D013154:Spleen / Q000187:drug effects* / Q000473:pathology
chemical_list: D000477:Alkylating Agents; D008770:Methylnitrosourea