title: Effect of administration of lovastatin on the development of late pulmonary effects after whole-lung irradiation in a murine model.
abstract: Our group's work on late radiation effects has been governed by the hypothesis that the effects observed in normal tissues are a consequence of multicellular interactions through a network of mediators. Further, we believe that inflammation is a necessary component of this process. We therefore investigated whether the recruitment of mononuclear cells, observed during the pneumonitic period in the irradiated normal lung, is dependent on the expression of chemokines, notably Mcp1. Since statins have been shown to reduce chemokine expression and inflammatory cell recruitment, we specifically examined whether statins could be used to reduce monocyte recruitment. Mice received 15 Gy whole-lung irradiation; treated groups were administered lovastatin three times weekly starting either immediately or 8 weeks postirradiation. At subsequent intervals, animals were killed humanely, and cellular, mRNA and protein analyses were undertaken. Statin-treated animals demonstrated a statistically significant reduction in both macrophage and lymphocyte populations in the lung compared to radiation alone as well as improved rates of survival and decreased collagen content. In addition, ELISA measurements showed that radiation-induced increases in Mcp1 protein were reduced by statin treatment. Additional experiments are needed to assess whether statins offer a potential treatment for the amelioration of late effects in breast and lung cancer patients undergoing radiation therapy.
authors.affiliation: Department of Radiation Oncology, James P. Wilmot Cancer Center, University of Rochester, Rochester, NY 14642, USA. Jackie_Williams@urmc.rochester.edu
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Williams
authors.forename: Eric
authors.initials: E
authors.lastname: Hernady
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Johnston
authors.forename: Christina M
authors.initials: CM
authors.lastname: Reed
authors.forename: Bruce
authors.initials: B
authors.lastname: Fenton
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Finkelstein
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008148:Lovastatin / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000188:drug therapy* / Q000517:prevention & control*; D012119:Respiration / Q000187:drug effects / Q000528:radiation effects; D015996:Survival Rate
chemical_list: D008148:Lovastatin