The discussion centers on the toxicity of arsenic to silicon-based lifeforms, with participants concluding that arsenic is likely toxic due to its diverse mechanisms of action. Key mechanisms include oxidative stress, disruption of cellular respiration, and interference with biochemical pathways. The consensus is that, given arsenic's established toxic effects on carbon-based life, it is reasonable to assert that silicon-based lifeforms would also be adversely affected. This conclusion is supported by various studies on arsenic's carcinogenic properties and cellular responses.
PREREQUISITESResearchers in astrobiology, toxicologists, and anyone interested in the biochemical effects of arsenic on various lifeforms.
Mechanisms of Toxicity
In this chapter, the subcommittee summarizes what is known about the mechanisms of toxicity for arsenic. The chapter is divided into two major sections-cancer and noncancer effects. In the cancer section, the subcommittee summarizes results from in vivo and in vitro bioassays designed to investigate the role of arsenic and metabolites of arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as tumor promoters and initiators. That summary is followed by a discussion of the data on modes of action for arsenic-induced carcinogenesis and how those data can help delineate the slope of the dose-response curve at low exposure concentrations. In the noncancer section, the subcommittee summarizes what is known about the mechanisms of action leading to noncancer effects. The potential relationships between mechanisms of arsenic-induced cell injury or cell death and carcinogenic processes are discussed with particular attention to the inter-relationships between arsenic-induced formation of reactive oxygen species or oxidative stress and chromosomal damage in target-cell populations. The roles of other documented arsenic-induced cellular responses, such as alterations in the heme biosynthetic pathway, alterations in cellular gene expression, and inhibition of DNA-repair enzyme activities, are discussed as components of the broad spectrum of cellular responses to arsenic exposure.
Mode of Action.
Enzymology and toxicology of inorganic arsenic (H.V. Aposhian, R.A. Zakharyan et al.). Structural proteomics of arsenic transport and detoxification (Z. Liu, R. Mukhopadhyay et al.). A novel S-adenosylmethionine-dependent methyltransferase from rat liver cytosol catalyzes the formation of methylated arsenicals (S.B. Waters, S. Lin et al.). Metabolism of arsenic and gene transcription regulation: Mechanism of AP-1 activation by methylated trivalent arsenicals (Z. Drobná, I. Jaspers, M. Stýblo). Effect of antioxidants on the papilloma response and liver glutathione modulation mediated by arsenic in Tg.AC transgenic mice (K. Trouba, A. Nyska et al.). Application of filter arrays in the study of arsenic toxicity and carcinogenesis (Jie Liu, Hua Chen et al.). Regulation of redox and DNA repair genes by arsenic: Low dose protection against oxidative stress? (E.T. Snow, Yu Hu et al.). Carcinogenicity of dimethylarsinic acid (DMA) (S.M. Cohen, C. Le et al.). Urinary speciation of sodium arsenate in folate receptor knockout mice (O. Spiegelstein, X. Lu et al.). Some chemical properties underlying arsenic's biological activity (K.T. Kitchin, K. Wallace, P. Andrewes). Arsenic metabolism in hyperbilirubinemic rats: distribution and excretion in relation to transformation (K.T. Suzuki, T. Tomita et al.). Incorporating mechanistic insights in a Pbpk model for arsenic (E.M. Kenyon, M.F. Hughes et al.).