The effects of epoxidized xenobiotics on mitogen responsiveness and antibody-producing ability of murine spleen cells in vitro

Abstract

The effects of benzo( a)pyrene [B( a)P], B( a)P-4,5- and 7,8-dihydroepoxide, (+)-B( a)P-7,8-diol,(−)-B(a)P-7,8-diol, cholestan-5α,6α-epoxy-3β-ol, cholestan-5β,6β-epoxy-3β-ol, cholestantriol and styrene oxide, on the in vitro mitogen responses and antibody-producing ability of mouse spleen cells were evaluated. B( a)P suppressed the plague-forming cell (PFC) response to T-cell dependent antigen sheep red blood cells (SRBC), but had no effect on the proliferative response to mitogens (phytohemagglutinin, concanvalin A and lipopolysaccharides) except a slight but significant increase to concanavalin A at lower doses. B( a)P-4,5- and 7,8-dihydroepoxides completely inhibited the proliferative response at concentrations exceeding 10 −6 M, but lower concentrations were without any effect. These two epoxides also suppressed the PFC response at concentration ⩾10 −5 M. This was accompanied by reduced cell viability. (+)-B( a)P-7,8-diol produced a dose-dependent suppression of PFC response to SRBC without altering the cell viability. The proliferative response was inhibited only at concentration ⩾10 −4 M. In contrast, (−)-B(a)P-7,8-diol has no effect on the PFC response and suppressed the proliferative response only at concentration of ⩾10 −5 M. Cholestan compounds had no effect on the plaque-forming cell response at concentrations ⩽10 −5 M. The effects on the proliferative response to mitogens were inhibitory and stimulatory depending upon the dose used. Styrene oxide neither inhibited the PFC nor the proliferative responses. The results of this study indicate that compounds with an electrophilically reactive epoxide moiety are cytotoxic at higher concentration, but have no uniform immunomodulatory effect on the in vitro parameters of immunological responsiveness.