Also, I know about eDuke, but I would like to play it in a "pure" DOS environment if I can. Thanks!
You do know that eDuke will play the game in a "pure" way? You can have all the modern lighting and graphics turned off and play it just as it plays in DOS. Though eDuke has a vastly better mouselook than the DOS game does.
As for the issue you are having, I've no idea, not heard of that one before. I used to have a similar issue when I played the DOS version from Windows 98, way back when I first played Duke Nukem. Whenever I descended into the sewer in the first level it would crash to Windows. That issue was a sound emulation issue that 3D Realms released a patch for, though. You could always try that patch. It's still on the 3D Realms site. http://www.3drealms.com/downloads.html
In the Duke Nukem 3D section look for the dnsndfx.exe patch.
That didn't work, but I think I fixed my problem. I never thought of running the setup program as administrator. I can change the resolution to whatever I want, but it doesn't seem to make a difference that I can immediately see. Ah well. I'm just used to tinkering with DOS games anyway.