title: Aging is associated with increased clonogenic potential in rat liver in vivo.
abstract: Cancer increases with age and often arises from the selective clonal growth of altered cells. Thus, any environment favoring clonal growth per se poses a higher risk for cancer development. Using a genetically tagged animal model, we investigated whether aging is associated with increased clonogenic potential. Groups of 4-, 12-, 18-, and 24-month-old Fischer 344 rats were infused (via the portal vein) with 2x10(6) hepatocytes isolated from a normal syngenic 2-month-old donor. Animals deficient in dipeptidyl-peptidase type IV (DPP-IV-) enzyme were used as recipients, allowing for the histochemical detection of injected DPP-IV+ cells. Groups of animals were sacrificed at various times thereafter. No growth of DPP-IV+ transplanted hepatocytes was present after either 2 or 6 months in the liver of rats transplanted at young age, as expected. In striking contrast, significant expansion of donor-derived cells was seen in animals transplanted at the age of 18 months: clusters comprising 7-10 DPP-IV+ hepatocytes/cross-section were present after 2 months and were markedly enlarged after 6 months (mean of 88+/-35 cells/cluster/cross-section). These results indicate that the microenvironment of the aged liver supports the clonal expansion of transplanted normal hepatocytes. Such clonogenic environments can foster the selective growth of pre-existing altered cells, thereby increasing the overall risk for cancer development associated with aging.
authors.affiliation: Department of Biomedical Sciences and Biotechnology, Section of Experimental Pathology, University of Cagliari, Cagliari, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pasciu
authors.forename: Stefania
authors.initials: S
authors.lastname: Montisci
authors.forename: Marianna
authors.initials: M
authors.lastname: Greco
authors.forename: Silvia
authors.initials: S
authors.lastname: Doratiotto
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pitzalis
authors.forename: Paolo
authors.initials: P
authors.lastname: Pani
authors.forename: Sergio
authors.initials: S
authors.lastname: Laconi
authors.forename: Ezio
authors.initials: E
authors.lastname: Laconi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002455:Cell Division; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000502:physiology / Q000637:transplantation; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology* / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D013997:Time Factors; D014185:Transplantation, Isogeneic
chemical_list: D018819:Dipeptidyl Peptidase 4