IIRC the RS-232 spec is something like min. +/-3V and (absolute) max. +/-25V. Adding something like a MAX232 would probably be a good idea.
Does it work with USB-serial interfaces? I don't think all(most?) of them implement handshaking.
They usually do implement handshaking, but the packetised nature of USB means that relative timings can get very screwed.
from my limited knowledge, the handshaking is done in chip level, not the chip's serial out pins. regarding timing, the detailed eeprom datasheet explanation can indicates if usb implementation is possible. and again from my limited knowledge, if its less than 64Bytes data at a time (62 actually), i think its possible, since i've done it with the ft232.