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Toxic effects of methyl methanesulfonate (MMS) on activated macrophages from chickens
M A Qureshi1, S E Bloom, J W Hamilton
1Department of Poultry and Avian Sciences, Cornell University, Ithaca, NY 14853.
Abstract:
Adherent peritoneal exudate cells rich in macrophages were harvested from Cornell K-strain chickens 42 hr after i.p. stimulation with Sephadex G-50. Glass-adherent monolayers were obtained on coverslips and subjected to in vitro exposure to methyl methanesulfonate (MMS) at various doses for 1 hr. Solvent (0.17% ethanol final concentration) and sham (RPMI 1640 growth media) exposures were also performed. At selected times after exposure, the macrophages were analyzed for cell viability, adherence, DNA damage, and functional activity. Although MMS doses of 5 x 10(-3) M and 1 x 10(-3) M concentrations resulted in significant cytoxicity, 2 x 10(-4) M had no significant cytotoxic effect. However, this exposure resulted in DNA damage as measured by alkaline elution. Concomitant with the DNA damage was a significant decrease in the phagocytic activity of macrophages. Repair of MMS-induced DNA lesions in macrophages was indicated by a normal DNA alkaline elution profile 10 hr postrecovery. Functional activity of cells also returned to normal levels. In contrast, the incidence of Fc receptor-positive cells detected by rosetting increased immediately after MMS exposure, and phagocytosis of opsonized SRBCs was not affected by 2 x 10(-4) M MMS treatment. Similarly, MMS treatment did not alter the acid phosphatase activity of macrophages. However, bactericidal ability of MMS-treated macrophages for unopsonized Escherichia coli was significantly depressed. These results suggest that the avian macrophage is a useful target cell for examining possible relationships between genotoxic and immunotoxic effects of environmental mutagens.
Insights
Avian macrophages exposed to methyl methanesulfonate (MMS) showed DNA damage and reduced bacterial killing, despite normal viability. These immune cells can reveal genotoxic and immunotoxic effects of environmental mutagens.
Area of Science:
- Immunotoxicology
- Genotoxicology
- Environmental Health
Background:
- Macrophages play a crucial role in immune responses and are potential targets for environmental toxins.
- Assessing the impact of genotoxic agents on macrophage function is vital for understanding immune system health.
Purpose of the Study:
- To investigate the effects of methyl methanesulfonate (MMS) on avian macrophage viability, DNA integrity, and functional activities.
- To explore the relationship between genotoxicity and immunotoxicity in macrophages exposed to environmental mutagens.
Main Methods:
- Peritoneal macrophages were harvested from chickens and exposed in vitro to varying doses of MMS.
- Analyses included cell viability, DNA damage (alkaline elution), phagocytosis, Fc receptor expression, acid phosphatase activity, and bactericidal ability.
Main Results:
- A non-cytotoxic dose of MMS (2 x 10(-4) M) induced significant DNA damage and decreased phagocytic activity and bactericidal ability against E. coli.
- Macrophage DNA repair occurred within 10 hours, restoring normal DNA profiles and phagocytic function.
- MMS exposure increased Fc receptor-positive cells but did not affect phagocytosis of opsonized SRBCs or acid phosphatase activity.
Conclusions:
- Avian macrophages exhibit susceptibility to MMS-induced DNA damage and functional impairment, indicating potential genotoxic and immunotoxic effects.
- The avian macrophage serves as a valuable model for studying the interplay between environmental mutagens and immune function.
- These findings highlight the importance of evaluating environmental agents for their combined genotoxic and immunotoxic potential on immune cells.