Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure.
Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing.
Theus
S A
SA
Department of Microbiology/Immunology, University of Arkansas for Medical Sciences, Little Rock 72205.
Tabor
D R
DR
Soderberg
L S
LS
Barnett
J B
JB
D000818:Animals; D002478:Cells, Cultured; D002706:Chlordan / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016897:Respiratory Burst / Q000187:drug effects; D015290:Second Messenger Systems / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000276:immunology
D009573:Nitrites; D002706:Chlordan; D007371:Interferon-gamma; D015544:Inositol 1,4,5-Trisphosphate; D006861:Hydrogen Peroxide