Immunocytotoxicity effects of polycyclic aromatic hydrocarbons on mouse lymphocytes

The in vivo effects of 3 polycyclic aromatic hydrocarbons (PAH): 3-methylcholanthrene (MCA), benzo[a]pyrene (BaP) and benzo[e]pyrene (BeP) on the ability of mouse lymphocytes to bind and kill target tumor cells in vitro were measured. C57 and C3H inbred mice were preimmunized with P815 tumor cells and then treated with a single i.p. injection of corn oil alone or with varying doses of the above PAH compounds (0.5-50 mg/kg body wt). At different post-injection times, antigen sensitized splenic lymphocytes (SL) and peritoneal exudate lymphocytes (PEL) were measured for binding and killing rates, using a single cell assay. MCA doses of 5 and 50 mg/kg inhibited SL: target cell binding 29-42% and PEL: target cell binding 23-60%. BaP had a similar significant dose dependent suppression on SL and PEL binding. Target cell killing rates by SL and PEL from MCA and BaP treated C57 and C3H mice were consistently suppressed at significant levels, compared to oil injected controls (P less than 0.05). On the other hand, binding and killing rates by SL and PEL from BeP treated mice showed an inconsistent and borderline significance at the above dose levels. When measured as a function of post-injection time of MCA, binding rates of SL from both mouse strains remained essentially unchanged after 10, 30 and 45 days. Target cell killing by SL from C3H and C57 mice, however, was suppressed 55-65% after 10-30 days post-injection. At 45 days post-injection, the capacity of SL to kill target tumor cells was restored to 64-70% of control values. The results suggest that binding is an early event that depends on dose, whereas target cell killing is a function of dose and post-injection time.