I would say off the top of my head that it's not a bad idea to prevent two users from editing the same file at the same time. Two users can open the same file of course, on the network, in OpenOffice.org; just not edit it.
You might consider breaking the spreadsheet into two or more, then creating one master spreadsheet and using Edit > Paste Special > Link, to bring them together. Linking between spreadsheets usually works pretty well. Then one user can get at one of the smaller spreadsheets and another user can get at the other one.
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