Suppression of immunity by some pesticides, xenobiotics, and industrial chemicals. <i>In vitro</i> model

Abstract

In recent years, attention has focused on suppression of immunity in immunocompromised patients. The definition of immunocompromise is impairment of the immune system caused by a disease or treatment. In addition to disease and treatment, other factors such as exposure to pesticides or toxic chemicals can damage the immune system. An in vitro test was used to assess the ability of monochloroacetic acid (MCA) (CAS number 79-11-8), dichloroacetic acid (DCA) (CAS number 79-43-6), trichloroacetic acid (TCA) (CAS number 76-03-9), and 2,2- dichloropropionic acid sodium salt (2,2-DCPANa, Dalapon) (CAS number 127-20-8) to suppress bacteriolysis by hen egg white lysozyme (HEWL). The system for bacteriolysis of Gram-negative bacteria Actinobacillus, Haemophilus, and Pasteurella in Tris-maleate buffer supplemented with EDTA and HEWL developed by Brondz et al. [1–4] was used to monitor bacteriolysis of Gram-negative bacteria in the Actinobacillus–Haemophilus–Pasteurella group. The halogenated acetic acid DCA is produced as a toxic artifact of the degradation of TCA and by disinfection of drinking and pool water and industrial waste. Nearly all humans consume DCA in drinking water during their lifetime; the concentration of DCA in drinking water can be higher than that associated with the upper-bound excess life-time cancer risk of 10^–4 (40μg/L) [5]. Lysozyme found in tears, saliva, nasal secretions, and excretions from all mucous membranes can break down the cell walls of bacteria and destabilize bacterial membranes. Lysozyme is involved in innate (nonspecific) immunity; the innate immune system is the first line of defense against invading organisms. Actinobacillus actinomy- cetemcomitans (ATCC29522), a Gram-negative bacterium whose primary ecological niche is the respiratory tract and oral cavity, provided the peptidoglycan substrate for HEWL. The optical density (OD) of a standardized suspension of <i>A. actinomycetemcomitans</i> decreased from 100% (OD 0.6 at 540 nm) to 23.5% after exposure to EDTA/HEWL for 50 min. After 50 min of exposure to 10.0 mg/mL of MCA, DCA, TCA, or 2,2-DCPANa as a supplement, EDTA/HEWL-induced lysis of A. actinomycetemcomitans decreased to 66.3%, 66.8%, 65.7%, and 73.6%, respectively. The aim of the presented study was the development of a model for measuring possible immunotoxic effects of chemicals, degradation products, xenobiotics and metabolites by these chemicals on the immune system. The method used is an in vitro bacteriolysis of Gram- negative bacterium induced by HEWL, described previously [1-4]. In the present study, several halogenated acids, MCA, DCA, and TCA, and the Na salt of 2,2-DCPA, exhibited immunosuppressive activity. The ability of MCA, DCA, TCA, and 2,2-DCPANa (Dalapon) to suppress HEWL induced bacteriolysis was demonstrated <i>in vitro.</i> document.