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Frontiers in Molecular Toxicology.

The science of toxicology sometimes gets a "bum rap" from chemists and biochemists, whose minds bring forth images of offices full of government bureaucrats and laboratories full of caged rodents. Regulatory decisionmaking and animal testing remain significant aspects of the discipline of toxicology and attract the most press attention. But the rush of modern advances in analytical chemistry, biochemical methodology, and molecular biology and genetics have transformed toxicology into a molecular science. Molecular toxicologists focus on mechanistic questions, especially on the interactions of xenobiotics (foreign substances such as pollutants, drugs, and carcinogens) with critical cellular target -- DNA, protein, specific enzymes, lipid membranes, and so on.

Until recently, the molecular toxicology research community lacked a "core" journal. Fundamental papers would appear in biochemical, biological, or medically-oriented journals. Most journals with the word "Toxicology" in the title were devoted to animal bioassays, pathological or histological investigations, and other far-from-molecular research. The new journal, Chemical Research in Toxicology, began publication in 1988, under the editorial guidance of Prof. L.J. Marnett, and has filled this need admirably. The American Chemical Society has ensured a consistently high scientific standard as well as excellent resources for production and distribution.

A feature of the new journal, since its inception, has been the publication of invited reviews. The present volume is a compilation of these reviews, 21 in number, collected from the first four years of publication. The articles are sorted into four topic areas: Toxic Agents and Their Actions; Enzymes of Activation, Inactivation, and Repair; Physical Methods (just two entries here, on NMR applications to DNA adduct analysis and the fluorescence line narrowing technique), and Macromolecular Modification.

The generally high quality of the submissions is evident; the reviews are by leading researchers in the field. Collected together, they cover a lot of ground: the index entries, running from "Aclacinomycin A" and "acute bovine pulmonary edema" to "Zero phonon transition", reflect the excitement of toxicology as a meeting ground for physical and biological scientists. On the other hand, the coverage is necessarily spotty, rather than exhaustive. For example, only three of the enzymes of biotransformation are reviewed (P-450, glutathione S-transferases, and glucuronosyl transferases). Some overlap among the reviews is to be expected. I found at least four separate references to the formation and reactions of benzo |a~ pyrene dihydrodiol epoxides (chapters 14, 15, 17 and 21); but only two of these appear in the index, which could lead to some frustration.

Unfortunately, the usefulness of this volume is diminished by the very rapid pace of progress in the field. The reviews have been reprinted verbatim, regrettably without the addition of appendices to bring them up to date. This compromises many of the reviews. Armstrong's 1991 article on Glutathione S-Transferases states that "it is quite likely that a ... high resolution |crystal~ structure ... will be available in the near future". Indeed, the first one appeared just a few months later (Reinemer et al., EMBO J. 10: 1997-2005, 1991). Myles and Sancar's comprehensive 1989 review on DNA Repair pre-dates the recent breakthroughs in cloning the human genes for Fanconi's anemia and several of the xeroderma pigmentosum complementation groups (reviewed by Barnes, Nature 359: 12-13, 1992). The final contribution on Cancer Suppressor Genes, published in Jan. 1989, has probably fared worst of all. The discovery of the role of p53 mutations in human and animal carcinogenesis has been the headline news of cancer research in the 1990's, and research is "at fever pitch" (Lane, Nature 358: 15-16, 1992), but the story unfolded right after the present volume's review was written.

In summary, this collection contains valuable background pieces. But one hesitates to recommend them to graduate students looking for a place to begin their term paper research; at least, they had better also seek out the 1992 literature. Perhaps a better approach would be an annual slim volume, along the lines of the J. Biol. Chem compendium of mini-reviews.
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Author:Josephy, P. David
Publication:Canadian Chemical News
Article Type:Book Review
Date:May 1, 1993
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