Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white.
Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.
Ponnaiya
B
B
Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch at Galveston 77555-0656, USA.
Cornforth
M N
MN
Ullrich
R L
RL
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002478:Cells, Cultured; D002842:Chromatids / Q000528:radiation effects / Q000648:ultrastructure; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000528:radiation effects* / Q000648:ultrastructure; D004260:DNA Repair / Q000235:genetics; D004198:Disease Susceptibility; D004848:Epithelium / Q000528:radiation effects / Q000648:ultrastructure; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D008321:Mammary Glands, Animal / Q000528:radiation effects* / Q000648:ultrastructure; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics*; D008810:Mice, Inbred C57BL / Q000235:genetics*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*