Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure

• Published in: Agents and actions Vol. 37; no. 1-2; p. 140
• Main Authors: Theus, S A, Tabor, D R, Soderberg, L S, Barnett, J B
• Format: Journal Article
• Language: English
• Published: Switzerland 01.09.1992
• Subjects: Animals; Cells, Cultured; Chlordan - toxicity; Cytotoxicity, Immunologic - drug effects; Female; Hydrogen Peroxide - metabolism; Inositol 1,4,5-Trisphosphate - metabolism; Interferon-gamma - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred BALB C; Nitrites - metabolism; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Burst - drug effects; Second Messenger Systems - drug effects; Tumor Cells, Cultured - immunology
• ISSN: 0065-4299
• DOI: 10.1007/BF01987903

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.