Mutagenesis by
chloramines and
hypochlorous acid (HOCl) was studied to determine whether these agents could contribute to the mutagenic and potentially carcinogenic activity of stimulated leukocytes and whether environmental exposure to these agents is a cause for concern. Mutagenic activity was measured using the S. typhimurium TA97a, TA100 and TA102 tester strains. Because
chloramines and HOCl are bactericidal, react rapidly with cell components, and can destroy the
histidine and
biotin required for the mutagenesis assay, activity can't be compared directly with that of less toxic or reactive agents. Nevertheless,
chloramines were mutagenic when tested under appropriate conditions. TA100 was the most sensitive strain, and the most active
mutagens were lipophilic dichloramines (RNCl2) including derivatives of
histamine,
ethanolamine and
putrescine. Lipophilic monochloramines (RNHCl) such as
histamine-monochloramine and NH2Cl were less active. Hydrophilic
chloramines such as
taurine-
chloramines had low activity, and HOCl was inactive. The metabolic state of the bacteria was critical.
Chloramines were mutagenic when added to bacteria with
glucose at 37 degrees C, but killing predominated when
chloramines were added at 4 degrees C or 25 degrees C, or at 37 degrees C without
glucose. Production of
chloramines and HOCl by leukocytes in vivo could contribute to the association of chronic
inflammation and
cancer as a result of: (1) the entry of membrane-permeable
chloramines into normal cells followed by attack on intracellular components including
DNA, and (2) the production of secondary
mutagens such as compounds with carbonyl groups or
carbon-
chlorine bonds. On the other hand, chlorination of water supplies is perhaps more likely to destroy than create
mutagens, and
chloramines from the environment are unlikely to penetrate the skin and mucous membranes.