You're going to have trouble with this scenario. There's no good portable way to check if a file is being modified by someone else, especially if you're dealing with network mounted filesystems of any flavor. (And no, lsof isn't a good portable way, but you might check its man page if it's available anyway.)

The most secure method would be to centralize all read-write responsibilities to one process, such as a daemon. That's what databases are: one process that can manipulate the files in a centralized way.

Barring that, you'll have to erect some systems involving baling wire and twine. Er, I mean chmod, rename and/or creating/unlinking auxiliary files. The only benefit to these operations is that they are, for the most part, atomic on all useful filesystems.

As for flock(), it's not even guaranteed to work. It's a "suggestion" or "advisory" and not a stable effective lock. If it works, great, but don't count on it working in all situations.