[Concise history of toxicology - from empiric knowledge to science]. / A toxikológia rövid története ­ a tapasztalattól a tudományig.

Toxicology is a science of poisonings by xenobiotics and endogenous physiological changes. Its empiric roots may be traced back to the emerging of the human race because the most important pledge of our predecessors' survival was the differentiation between eatable and poisonous plants and animals. In the course of social evolution, there were three main fields of using poisons: 1) hunting and warfare, 2) to settle social tensions by avoiding military conflicts through hiding strategy of eliminating enemies by toxic substances, 3) medicines applied first as anti-poisons and later by introducing strong substances to defeat diseases, but paradoxically active euthanasia is also a part of the whole story. The industrial revolution of the 19th century changed the sporadic occupational diseases to mass conditions. Later the chemical industry and subsequently the mass production of synthetic materials turned out as a global environmental catastrophe. This latest change initiated the emerging of ecological toxicology which is a future history of the concerning ancient science. Orv Hetil. 2018; 159(3): 83-90.

[From metabolism to comparative biochemistry of toxic organophosphorus compounds. To the 100th anniversary from the birth of V. I. Rozengart].

The main stages of the scientific biography of Professor Victor losifovich Rozengart are exposed: his works on muscle bioenergetics, discovery of the pathway of creatinine synthesis, his development of novel concepts of pathways of metabolism of organophosphorus xenobiotics, creation of biochemical grounds of selective toxicity as well as studies in the new field whose one of its founders he is--comparative biochemistry of toxic organophosphorus compounds.

Tales of two similar hypotheses: the rise and fall of chemical and radiation hormesis.

This paper compares the historical developments of chemical and radiation hormesis from their respective inceptions in the late 1880's for chemical hormesis and early 1900's for radiation hormesis to the mid 1930's to 1940 during which both hypotheses rose to some prominence but then became marginalized within the scientific community. This analysis documents that there were marked differences in their respective temporal developments, and the direction and maturity of research. In general, the formulation of the chemical hormesis hypothesis displayed an earlier, more-extensive and more sophisticated development than the radiation hormesis hypothesis. It was able to attract prestigious researchers with international reputations from leading institutions, to be the subject of numerous dissertations, to have its findings published in leading journals, and to have its concepts incorporated into leading microbiological texts. While both areas became the object of criticism from leading scientists, the intensity of the challenge was greatest for chemical hormesis due to its more visible association with the medical practice of homeopathy. Despite the presence of legitimate and flawed criticism, the most significant limitations of both chemical and radiation hormesis and their respective ultimate undoing were due to their: (1) lack of development of a coherent dose-response theory using data of low dose stimulation from both the chemical and radiation domains; (2) difficulty in replication of low dose stimulatory responses without an adequate study design especially with respect to an appropriate number and properly spaced doses below the toxic threshold; (3) modest degree of stimulation even under optimal conditions which was difficult to distinguish from normal variation; and (4) lack of appreciation of the practical and/or commercial applications of the concepts of low dose stimulation.

Forty years of cytochrome P450.

The term "cytochrome P450" first appeared in literature in 1962. It was a microsomal membrane-bound hemoprotein without known physiological functions at that time and was characterized by a unique 450-nm optical absorption peak of its carbon monoxide-bound form, which was originally reported as the spectrum of a novel "microsomal carbon monoxide-binding pigment" in 1958. Elucidation of its function as the oxygenase in 1963 triggered a rapid expansion of research on this hemoprotein. Annual numbers of the published papers dealing with cytochrome P450, which were listed in Biological Abstracts, increased from 60 in 1970 to 500 in 1980, 900 in 1990, and 1500 in 1997. Cytochrome P450 is now regarded as the collective name of a large family of hemoproteins, "cytochrome P450 superfamily, "which seems to have diversified from a single ancestral protein to many forms during the course of biological evolution and is distributed widely among various forms of life from animals and plants to fungi and bacteria. Multicellular eukaryotic organisms including animals and plants have about 100 or more P450 genes in their genomes, and those many P450 genes are expressed tissue specifically and developmental stage specifically, indicating their diverse physiological functions. In mammals, various P450s participate in the biosynthesis and metabolism of sterols and steroid hormones and the metabolism of various lipid biofactors including eicosanoids, vitamin D3, and retinoids. Oxidative metabolism of foreign hydrophobic compounds as the first step of their excretion from the animal body is apparently another major function of cytochrome P450, which protects animals from noxious foreign compounds, man-created and natural.