Micronuclei induced by radon and its progeny in deep-lung fibroblasts of rats in vivo and in vitro.
Genotoxic damage induced by radon and its progeny was investigated using the micronucleus assay in deep-lung fibroblasts to compare the response induced in vitro with that induced from inhalation of radon and its progeny in vivo. Male Wistar rats were exposed to 0, 115, 213 and 323 working-level months (WLM) of radon and its progeny by inhalation. After sacrifice, the cells were isolated and grown in culture, and the frequency of micronuclei was determined. A linear increase in the frequency of micronuclei was measured as a function of exposure [micronuclei/1000 binucleated cells = (29 +/- 9) + (0.47 +/- 0.04) WLM]. To compare exposure in WLM to dose in mGy, and to study how cell proliferation influences the way inhalation of radon and its progeny induces micronuclei, lung fibroblasts were isolated and exposed in vitro to graded doses from radon and its progeny after either 16 or 96 h in tissue culture. Cell cycle stage at the time of exposure was determined using flow cytometry. Primary lung fibroblasts exposed as either nondividing or dividing cells showed dose-dependent increases in micronuclei [micronuclei/1000 binucleated cells = (33 +/- 40) + (593 +/- 68)D and micronuclei/1000 binucleated cells = (27 +/- 69) + (757 +/- 88)D, respectively, where D is dose in Gy]. Results showed no significant influence (P = 0.20) of cell proliferation at the time of exposure on the frequency of micronuclei induced by radon and its progeny. Comparing dose-response relationships for nondividing cells to the exposure response for cells exposed by inhalation of radon and its progeny, it was estimated that a 1-WLM exposure in vivo caused the same amount of cytogenetic damage as produced by 0.79 mGy in vitro. In vivo/in vitro research using the micronucleus assay in lung fibroblasts serves as a powerful tool to estimate effective dose to cells in the respiratory tract after inhalation of radon and its progeny. Such studies form the basis for understanding the relationship between exposure, dose and biological damage.
Khan
M A
MA
Pacific Northwest Laboratory, Department of Biology and Chemistry, Richland, Washington 99352.
Cross
F T
FT
Jostes
R
R
Hui
E
E
Morris
J E
JE
Brooks
A L
AL
D000280:Administration, Inhalation; D000818:Animals; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000528:radiation effects / Q000648:ultrastructure; D008168:Lung / Q000528:radiation effects* / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects* / Q000648:ultrastructure; D015162:Micronucleus Tests; D011886:Radon / Q000008:administration & dosage; D017687:Radon Daughters / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D017687:Radon Daughters; D011886:Radon