A novel technique is described for the evaluation of membrane integrit
y in isolated nuclei. Membrane integrity is assessed by measuring nucl
ear fragility in response to high salt conditions. Salt-induced disrup
tion of the nuclear membrane is followed by spectrophotometric monitor
ing of released nucleotides. The assay is based on determining the amo
unt of salt necessary to induce release of 50% of the total pool of re
leasable nucleotides. This allows semiquantitative comparison of relat
ive nuclear membrane strength or integrity of different samples in res
ponse to high salt conditions. In this manner, the effects of altered
nuclear membrane composition or metabolism on membrane integrity may b
e monitored.