title: Normal hepatocyte transplantation delays the emergence of chemically induced preneoplastic nodules in rat liver.
abstract: Cancer often arises in a background of chronic tissue damage. It is also increasingly appreciated that such an injured tissue microenvironment might foster the selective emergence of altered cells, leading to neoplasia. Accordingly, reversal of chronic tissue damage could represent  a potential strategy to counteract neoplastic disease. In these studies, we aim to investigate whether transplantation of normal cells in the context of an injured, neoplastic-prone microenvironment might impact on the evolution of the carcinogenic process. A rat model of chemically induced  hepatocarcinogenesis was used. Animals were given a single dose of diethylnitrosamine (DENA), followed by two injections of retrorsine (RS), a pyrrolizidine alkaloid that imposes a persistent block on hepatocyte cell cycle. At the end of this protocol, rats were either given no further treatment  or injected, via the portal circulation, with 4 million normal hepatocytes isolated from a syngenic donor. After 3 months, rats given DENA+RS alone displayed numerous discrete nodular lesions (up to 30 per liver), ranging 1 to 3 mm in size. On the other hand, in animals receiving DENA+RS and  transplantation, donor hepatocytes were able to repopulate over 50% of the host liver, as expected. Most importantly, both the number and the size of hepatocyte nodules were greatly reduced in these animals (percent nodular area was 1.8 ± 0.3, down from a control value of 8.5 ±  2.8). The above data indicate that strategies aimed at reestablishing a normal tissue microenvironment might be relevant to the management of neoplastic disease.
authors.affiliation: Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Serra
authors.forename: Silvia
authors.initials: S
authors.lastname: Doratiotto
authors.forename: Fabio
authors.initials: F
authors.lastname: Marongiu
authors.forename: Ezio
authors.initials: E
authors.lastname: Laconi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004052:Diethylnitrosamine / Q000494:pharmacology*; D022781:Hepatocytes / Q000637:transplantation*; D007150:Immunohistochemistry; D008099:Liver; D008113:Liver Neoplasms / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D011763:Pyrrolizidine Alkaloids; D004052:Diethylnitrosamine; C003300:retrorsine