Melanin‐producing Cryptococcus and Aspergillus are highly invasive and can suppress or escape the immune system of the host. Since non‐melanin‐producing strains do not affect the immune system, melanin may play a role in immune system suppression. Artificial melanin synthesized using conventional methods is insoluble, making structural and functional analysis of this chemical difficult. In this study, we describe a melanin solubilization method based on polymerization of homogentisic acid (solubilizing component) and an equivalent amount of L‐DOPA in the presence of laccase. In addition, we investigated the effect of melanin on the immune system. Homogentisic acid and L‐DOPA mixed melanin (HALD), the synthetic solubilized melanin, did not exert a cytotoxic effect on mouse macrophages. HALD suppressed cytokine and reactive oxygen species production by macrophages when they were stimulated by fungal components. HALD also suppressed the phagocytosis of fungal components by macrophages. These results suggest that HALD can suppress the function of macrophages without causing cytotoxicity.

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In order to elucidate the preventive mechanism of molybdenum (Mo) against carcinogenesis of N-nitroso compounds, the effects of in vivo Mo-pretreatment on N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in rats were examined. Effects of in vitro Mo-pretreatment on NDEA-induced DNA strand breaks and fluctuation of the cytosolic free Ca levels in rat hepatocytes were also investigated. Male Wistar rats weighing 170-190 g were pretreated with 10 ppm Mo as Na2MoO4 in deionized drinking water for 21 days, and on day 22, they were exposed to NDEA (50 mg/kg body weight, once, i.p.). 3 and 5 days after NDEA exposure, serum lactic dehydrogenase (LDH) activity, and hepatic calcium (Ca) content and lipid peroxidation levels were evaluated. In vivo Mo-pretreatment prevented NDEA-induced elevations in serum LDH activity and liver Ca content but increased hepatic lipid peroxidation levels. Hepatocytes isolated from rats pretreated with sodium phenobarbital (80 mg/kg body weight, i.p., once a day for 3 days) were exposed to NDEA (0, 100, 250 and 500 μM) in vitro for 30 min at 37°C. NDEA treatment caused DNA strand breaks and a perturbation of cytosolic free Ca level. However, in vitro Mo-pretreatment (20 μM, 20 min at 37°C) suppressed the NDEA-induced DNA damage and disruption of intracellular Ca homeostasis. These results suggest Mo protected against NDEA-induced hepatotoxicity by stimulating the metabolism of the nitroso compound via a nontoxic pathway (denitration) while preventing DNA damage connected with alteration in cytosolic free Ca levels. Thus, the general protective action of Mo against N-nitroso compound-induced carcinogenesis may be explained by a common mechanism.