Potential role of alpha-synuclein and metallothionein in lead-induced inclusion body formation.

Lead (Pb) produces aggresome-like inclusion bodies (IBs) in target cells as a toxic response. Our prior work shows metallothionein (MT) is required for this process. We used MT-I/II double knockout (MT-null) and parental wild-type (WT) cell lines to further explore the formation process of Pb-induced IBs.

Mineral arsenicals in traditional medicines: orpiment, realgar, and arsenolite.

Mineral arsenicals have long been used in traditional medicines for various diseases, yet arsenic can be highly toxic and carcinogenic. Arsenic in traditional medicines typically comes from deliberate addition for therapeutic purposes, mainly in the form of mineral arsenicals, including orpiment (As2S3), realgar (As4S4), and arsenolite (contains arsenic trioxide, As2O3). Inorganic arsenic is now accepted in Western medicine as a first line chemotherapeutic agent against certain hematopoietic cancers.

Mercury in traditional medicines: is cinnabar toxicologically similar to common mercurials?

Mercury is a major toxic metal ranked top in the Toxic Substances List. Cinnabar, which contains mercury sulfide, has been used in Chinese traditional medicines for thousands of years as an ingredient in various remedies, and 40 cinnabar-containing traditional medicines are still used today. Little is known about toxicology profiles or toxicokinetics of cinnabar and cinnabar-containing traditional medicines, and the high mercury content in these Chinese medicines raises justifiably escalations of public concern.

Cadmium and cancer of prostate and testis.

Cancer of the prostate is an important and potentially fatal disease in humans but the etiology is yet undefined. Cadmium and cadmium compounds are known to be human carcinogens based on findings of increased risk to lung cancer among exposed workers, but a relationship between cancer of the prostate and/or testis in humans is unclear in spite of suggestive results in rats. Parenteral administration or oral exposure to cadmium can result in proliferate lesions and tumors of the prostate in rats.

Metallothionein-I/II double knockout mice are hypersensitive to lead-induced kidney carcinogenesis: role of inclusion body formation.

Lead is an environmental nephrotoxicant and probable human carcinogen. Elucidating factors predisposing populations to lead toxicity is an important public health issue. Recently, we found that metallothionein-I/-II double knockout (metallothionein-null) mice that are unable to produce the major forms of metallothionein do not produce lead inclusion bodies, which are thought to mitigate lead toxicity, and were sensitive to the subchronic toxic effects of lead exposure (10 weeks), showing modestly diminished renal function and nephromegaly compared with wild-type (WT) mice.

The metallothionein-null phenotype is associated with heightened sensitivity to lead toxicity and an inability to form inclusion bodies.

Susceptibility to lead toxicity in MT-null mice and cells, lacking the major forms of the metallothionein (MT) gene, was compared to wild-type (WT) mice or cells. Male MT-null and WT mice received lead in the drinking water (0 to 4000 ppm) for 10 to 20 weeks. Lead did not alter body weight in any group.