Immunosuppressive effects of 2-acetylaminofluorene and 2-aminofluorene on murine splenocytes culture

The immunosuppressive effects of 2-acetylaminofluorene (AAF) and 2-aminofluorene (AF) were studied in BALB/c mouse splenocyte culture. Direct addition of AAF and AF to the splenocyte culture produced a dose-related suppression of the in vitro antibody response to sheep erythrocytes(SRBC), DNP-Ficoll, and lipopolysaccharide(LPS). AAF and AF also produced suppression on lymphoproliferative responses to LPS and concanavalin A(Con A). The immunosuppressive effects of AAF and AF, however, were diminished when AAF and AF were incubated in the splenocyte-hepatocyte coculture system for 4 hr. When hepatocyte cultures were pretreated with SKF 525A, a cytochrome P-450 inhibitor, before coculture with spleen cell along with AAF and AF, the suppression of in vitro antibody response reappeared. Meanwhile, both AAF and AF produced a dose-related DNA single-strand breaks in spleen cells only if AAF and AF were treated to spleen cells cocultured with hepatocytes. These results indicate that the immunosuppression by AAF and AF is not mediated by the reactive metabolites implicated to DNA damage.