Journal Article

Induction of genomic instability in normal human bronchial epithelial cells by <sup>238</sup>Pu α-particles

Christopher H. Kennedy, Charles E. Mitchel, Noelle H. Fukushima, Robin E. Neft and John F. Lechner

in Carcinogenesis

Volume 17, issue 8, pages 1671-1676
Published in print August 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.8.1671
Induction of genomic instability in normal human bronchial epithelial cells by 238Pu α-particles

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Pulmonary deposition of αparticle-emitting radon daughters is estimated to account for 10% of all lung cancer deaths in the USA. However, the nature and timing of early (preneoplastic) genetic alternations in radon-associated lung cancer are still relatively uncertain. The purpose of this investigation was to determine whether genomic instability occurs after exposure of cultured normal human bronchial epithelial cells to six equal, fractionated doses of αparticles (total doses 2–4 Gy). Two weeks after the final exposure, foci of phenotypically altered cells (PACs) were detected in 0, 63 and 77% of control, low and high dose cultures respectively. Of these, 18% exhibited extended life spans relative to unexposed controls. Elevated frequencies of binucleated cells (BNCs), a marker of genomic instability, were observed in 60 and 38% of the PAC cultures from the low and high dose groups respectively. The micronucleus assay also showed evidence of genomic instability in 40 and 38% of PAC cultures from the low dose and high dose groups respectively. No changes in microsatellite length, another marker of genomic instability, were detected in any of the PAC samples with the 28 markers used for this assay. However, one PAC (L2) showed a hemizygous deletion at 9p13.3. Another PAC (H9), which exhibited the highest frequency of cells containing micronuclei (MN), exhibited a hemizygous detection at 7q31.3. Each loss may represent a stable mutation that resulted either directly from irradiation or later in progency of exposed cells because of α-particle-induced genomic instability. The fact that elevated levels of BNCs and MN were present in the progency many generations after irradiation indicates that the genetic alternations detected with these two markers were not a direct consequence of radiation exposure, but of resulting genomic instability, which may be an early change after exposure to α-particles.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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