In vitro effects of MOCA and dapsone on rat hepatic and splenic immune cells.
The industrial curing agent 4,4'-methylene-bis(2-chloroaniline) (MOCA) and the structurally related medicinal agent 4,4'-sulphonyldianiline (dapsone), are two commonly used aromatic amine compounds and documented animal carcinogens. In this study the effects of in vitro exposure to MOCA and dapsone (over a dose range of 1-200 microM on spleen and liver immune cell functions were investigated. MOCA exposure caused a dose-dependent inhibition of natural immune activities (i.e. natural killer, NK and natural P815 killer, NPK) and mitogen-stimulated proliferation of T- and B-lymphocytes, with 50% inhibition (IC50) of splenic-cell activities occurring at 145, 85, 21 and 31 microM, respectively. Liver NK and NPK activities were less sensitive to MOCA exposure and exhibited higher IC50's of 165 and 160 microM, respectively. Dapsone exposure slightly enhanced both T- and B-cell mitogenesis at low doses (1 microM) but decreased B-cell mitogenesis at high doses (IC50 = 130 microM). Natural tumouricidal activities were generally unaffected by dapsone, whilst natural cytotoxic (NC) activity was unaffected by both compounds. These results indicate that MOCA is generally immunotoxic in vitro, and may have the potential to enhance the carcinogenic effects of its genotoxic metabolite by inhibiting the tumour surveillance activities of the immune system. The relationship between immune effects and the carcinogenicity of dapsone remains unclear.
Kelso
J M
JM
Key Centre for Applied and Nutritional Toxicology, RMIT University, Melbourne, Vic., Australia.
Bai
C L
CL
Ahokas
J T
JT
Wright
P F
PF
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002273:Carcinogens / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D003622:Dapsone / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008753:Methylenebis(chloroaniline) / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000890:Anti-Infective Agents; D002273:Carcinogens; D008753:Methylenebis(chloroaniline); D003622:Dapsone