A comparison of levels of intrinsic single strand breaks/alkali labile sites associated with human melanoma cell invasion.
Intrinsic levels of protein-free single strand breaks/alkali-labile sites in human melanoma cell populations of varying in vitro invasive capacity have been assayed with DNA filter elution methodology. DNA from two human melanoma cell lines, A375P and C8161, and from a subpopulation selected from A375P, A375P-5, were assayed to test the hypothesis that increased levels of DNA damage may be associated with the phenotype of increased invasive and metastatic capacities. The elution profiles obtained reveal statistically significant increases in the level of single strand breaks and/or alkali-labile sites (SSB/ALS) which correlate with increasing invasive and metastatic capacities. The increased levels of SSB/ALS in A375P-5 observed in freshly selected cells decline as these cells are maintained in culture. The stability of this A375P-5 phenotype correlates with previously reported levels of double minute chromosomes, an indicator of genomic instability. Alterations in average intrinsic levels of cellular lesions are therefore an additional factor to be considered in the phenotypic characterization of invasive and metastatic tumor cells and may reflect or contribute to the genomic instability characteristic of tumor cell populations.
Department of Biochemistry, University of Arizona, Tucson 85724.
L C
LC
Meade-Tollin
B L
BL
Pipes
S J
SJ
Anderson
E A
EA
Seftor
M J
MJ
Hendrix
D000468:Alkalies / Q000378:metabolism; D001485:Basement Membrane / Q000502:physiology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D000468:Alkalies; D004273:DNA, Neoplasm