title: Bound PCNA in nuclei of primary rat tracheal epithelial cells after exposure to very low doses of plutonium-238 alpha particles.
abstract: Bystander effects from ionizing radiation have been detailed for a number of cell systems and a number of end points. We wished to use a cell culture/ex vivo rat model of respiratory tissue to determine whether a bystander effect detected in culture could also be shown in a tissue. Examination by immunofluorescence techniques of tracheal cell cultures after exposure to very low doses of alpha particles revealed a large proportion of cells with proliferating cell nuclear antigen (PCNA) bound in their nuclei. PCNA was selected as an end point because it is involved in both DNA repair and the changes in cell cycle that are typical of many reported bystander effects. Maximum response can be detected in up to 28% of the cells in sub-confluent cultures with a dose of only 2 mGy. At this dose less than 2% of the cell nuclei have experienced a particle traversal and less than 6% of the cells have experienced an alpha-particle traversal through either their nucleus or some part of their cytoplasm. The hypothesis that this bystander response in nontargeted cells is mediated through secreted factor(s) is presented, and supporting evidence was found using partial irradiation and co-culture experiments. Examination of the effect with excised pieces of trachea demonstrated a response similar to that seen in culture.
authors.affiliation: Medical Research Council, Radiation and Genome Stability Unit, Harwell, Oxfordshire, OX11 0RD, United Kingdom.
authors.forename: M A
authors.initials: MA
authors.lastname: Hill
authors.forename: J R
authors.initials: JR
authors.lastname: Ford
authors.forename: P
authors.initials: P
authors.lastname: Clapham
authors.forename: S J
authors.initials: SJ
authors.lastname: Marsden
authors.forename: D L
authors.initials: DL
authors.lastname: Stevens
authors.forename: K M S
authors.initials: KM
authors.lastname: Townsend
authors.forename: D T
authors.initials: DT
authors.lastname: Goodhead
mesh_terms: D000512:Alpha Particles; D000818:Animals; D024201:Bystander Effect / Q000502:physiology* / Q000528:radiation effects*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D008297:Male; D011005:Plutonium / Q000009:adverse effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011485:Protein Binding; D011829:Radiation Dosage; D051381:Rats; D011916:Rats, Inbred F344; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000528:radiation effects*; D014132:Trachea / Q000378:metabolism* / Q000528:radiation effects*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D011005:Plutonium