The effects of epoxidized xenobiotics on mitogen responsiveness and antibody-producing ability of murine spleen cells in vitro.
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-5 alpha,6 alpha-epoxy-3 beta-ol, cholestan-5 beta,6 beta-epoxy-3 beta-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 plaque-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, concanavalin 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 greater than or equal to 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 greater than or equal to 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 greater than or equal to 10(-5) M. Cholestan compounds had no effect on the plaque-forming cell response at concentrations less than or equal to 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Tomar
R S
RS
Department of Entomology, University of California, Riverside 92521-1037.
Lim
S
S
Gill
S S
SS
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000921:Antibody-Producing Cells / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004852:Epoxy Compounds / Q000633:toxicity*; D005260:Female; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D015262:Xenobiotics / Q000633:toxicity
D004852:Epoxy Compounds; D008934:Mitogens; D015262:Xenobiotics