Toxic effects of methyl methanesulfonate (MMS) on activated macrophages from chickens.

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.