ARSENIC IN THE SERA OF GALLIUM ARSENIDE-EXPOSED MICE INHIBITS BACTERIAL-GROWTH AND INCREASES HOST-RESISTANCE

The objective of the present investigations was to evaluate whether th e presence of gallium arsenide (GaAs) in the sera of exposed mice was sufficient to retard bacterial growth. Host resistance studies demonst rated that exposure to GaAs (50-200 mg/kg) produced an increased resis tance to Streptococcus pneumoniae and Listeria monocytogenes (50-1 00 mg/kg GaAs) when microbial challenge occurred 24 hr after exposure. In contrast, exposed mice exhibited a profound and dose-related decrease in resistance to the B16F10 melanoma. Serial dilutions of GaAs (0.039 -5 mg/ml) were added to BHI broth and cultures were innoculated with e ither S. pneumoniae or L. monocytogenes. GaAs slowed the growth of bot h organisms with a minimal inhibitory concentration (MIC) of 0.625 mg/ ml. Sera from mice euthanized at various time intervals after exposure to vehicle (0.05% Tween 80 in saline) or GaAs (200 mg/kg) was also ca pable of retarding the growth of both organisms with the maximal inhib ition noted for euthanization 24 hr after exposure. However, sera from GaAs-exposed mice (24 hr after exposure) was incapable of slowing the growth of the B16F10 melanoma. Addition of the arsenic-binding compou nd meso-2,3-dimercaptosuccinic acid (100 muM) to sera from mice expose d to GaAs followed by innoculation with L. monocytogenes resulted in g rowth of this organism, which was comparable to growth observed in veh icle cultures. These studies demonstrate that arsenic in the sera of G aAs-exposed mice is capable of exerting chemotherapeutic effects on S. pneumoniae and L. monocytogenes, but not the B16F10 melanoma. The pre sent investigations are important because they clearly demonstrate the intricate relationship between the action of the host to the pathogen and the action xenobiotics may produce on both the host and pathogen.