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Summary 1 After some false starts in which inactive plant substances were isolated, the isolation and identification of auxin as the growth substance at the meristems and of ethylene as the ripening agent in climacteric fruits represented outstanding achievements. 2 In early work, the non-localized origin of auxin at the meristem and its possible transport for coleoptile development were obscured by the superimposition on the results of physiological experiments of the idea of a close parallelism between the plant-growth substances and mammalian hormones. At that time, an absence of chemical instrumentation, suitable for measurement of the tissue levels, compounded the difficulty in interpreting available physiological evidence. 3 Member(s) of each of the five groups of naturally occurring plant-growth substances, namely the auxins, cytokinins, gibberellins, ethylene and the growth inhibitors, including abscisic acid, are biologically active at a concentration of 10 μm or less, however, and in this respect they would appear to qualify as candidate phytohormones. 4 The sensitivity of plant cells to phytohormones contributes to plant growth and development, and both the variations in sensitivity, for example, of wheat coleoptiles towards growth and the growth of the coleoptiles per se give parallel unimodal relationships with regard to time; the curve representing sensitivity precedes that for growth. A new graphical analysis implies that the growth sensitivity and growth rate functions are mutually interdependent. 5 The assumption is made in point 4 that growth substance complexes with receptor protein in growth-sensitive cells, and the concept of receptors would provide explanation for the obvious amplification of effects induced by growth substances. 6 Numerous biological situations occur in which the presence of significant amounts of plant hormone controls growth and development. In gravitropism and phototropism, tropistic curvature depends on the difference in physiological concentration of auxin on the two sides of the organ concerned. In infected tobacco plants, the cytokinin to auxin ratios for the tumours determine the kind of development (tumours and shoots, tumours only or tumours plus roots), which takes place. 7 Auxin-binding protein has been identified immunologically, and isolated. Work with hormone receptors for gibberellin does not afford unequivocal evidence for more than one primary site of action. Hitherto, no specific receptor protein is known for cytokinins. 8 Clear evidence derives, both from structure–activity relationships and from unimodal concentration–response curves, for receptor specificity to auxin action. There is also evidence for a structure–activity relationship in respect of the cytokinin series of compounds. 9 From the evidence (points 1–8), there emerges a picture of hormone-induced growth and development of plant cells, which have been made sensitive to hormone through the presence of specific receptor proteins. 10 That plant growth and developmental processes involve changes in gene expression would seem to follow from the totipotent nature of meristematic cells, which are capable of specialization in response to phytohormones. 11 Auxin regulates de novo synthesis of mRNAs encoding polypeptides essential to the auxin-induced early process of cell elongation. In fact, auxin regulates the concentrations of several authenticated mRNAs and proteins, for example, in elongating soyabean hypocotyl sections. 12 Furthermore, two cDNA clones, termed pJCW1 and pJCW2 have been isolated with the properties expected of mRNAs involved in the rate-limiting stage of cell elongation. The evidence suggests that the change in relative abundance of the JCW1 and JCW2 RNAs is an obligatory auxin-dependent response. Hence, the action of cytokinin in auxin-induced cell elongation would seem to be concerned with the inhibition of rate-limiting proteins, and in fact cytokinin inhibits protein synthesis in excised soyabean hypocotyl. 13 Biosystemic experiments on some rapid effects of synthetic auxin growth regulators on mRNA levels in vitro show that there is only partial similarity between those found in pea and soyabean spp. (Leguminosae). 14 Two identified sequences, namely TGATAAAAG and GGCAGCATGCA, of two auxin-regulated soyabean genes afford a means for determining whether the auxin-regulation of expression of these genes involves trans-acting regulatory factors. 15 The obligatory auxin-induced responses with regard to cell elongation and growth (q.v.) would seem to precede the somewhat mechanical growth properties by which auxin receptive cells secrete H+ and lower the pH to yield increased cell-wall plasticity. 16 In vertically oriented soyabean seedlings, auxin-regulated RNAs are distributed symmetrically in the elongating region of the hypocotyl, whereas in horizontally oriented seedlings the distribution becomes asymmetrical within a few minutes of horizontal gravitational stimulation. The dynamic expression of auxin-regulated genes is related to the morphogenetic response, initiated by re-distribution of endogenous auxin (point 6). 17 In the germination of seeds, the mobilization of food reserves requires hydrolytic enzymes and, in barley grains, gibberellic acid induces de novo biosynthesis of α-amylase and protease. The genetic implications are discussed, and the requirement of dicotyledonous and gymnospermous seeds for the presence of gibberellins is explored. 18 In ripening climacteric fruits, ethylene-induced change(s) in gene expression cause de novo biosynthesis of polygalacturonase, which degrades the cell-wall pectin fraction. 19 Accordingly, incontestible evidence has been mustered for the proposition that hormone-regulated plant growth and development involves hormone-regulated gene expression. 20 As well as the phytohormones, certain environmental factors, such as white light and stress (including anaerobiosis, chilling, heat shock, heavy metal exposure, u.v. light and wounding) have the capacity to regulate gene expression in plants at important stages in growth and development. Discussion at the genetic level focuses on changes produced by: 21 The synthesis of phytohormones is significant. For example, as u.v. light-induced regulation of genes produces enzymes for auxin synthesis, it may be responsible in seeds for the endospermal generation of auxins, concerned with the epicotyl/hypocotyl growth in the seedlings. 22 Hormones and certain environemental factors (q.v.) initiate some of the numerous stages in plant growth and development, but the regulatory factors are obscure in some other biological situations, such as: 23 Utilization of an appropriately re-constituted plant DNA polymerase i in vitro system might enable the type and frequency of misincorporation, produced by plant-growth factors, to be studied. Base-pair substitution changes were produced in strains of crop plant, made resistant to a specific herbicide by genetic engineering (see Hathway, 1989). It is feasible that auxin may behave as a reagent in the chemical sense to effect intramolecular change(s) in some of the sequences concerned, leading to the frame-shift changes observed (see Ainley et al., 1988).

Some six or so physiological systems, essential to normal mammalian life, are involved in poisoning; an intoxication that causes severe injury to any one of them could be life threatening. Reversible chemical reactions showing Scatchard-type binding are exemplified by CO, CN- and cyclodiene neurotoxin insecticide intoxications, and by antigen-antibody complex formation. Haemoglobin (Hb) molecular biology accounts for the allosteric co-operativity and other characteristics of CO poisoning, CN- acts as a powerful cytochrome oxidase inhibitor, and antigen binding in a deep antibody cleft between two domains equipped with epitopes for antigen-binding groups explains hapten-specific immune reactions. Covalent chemical reactions with second-order (SN2) kinetics characterize Hg and Cd poisonings, the reactions of organophosphates and phosphonates with acetylcholinesterase and neurotoxic esterase and the reaction sequence whereby Paraquat accepts electrons and generates superoxide under aerobic conditions. Indirect carcinogens require cytochrome P450 activation to form DNA adducts in target-organ DNA and cause cancer, but a battery of detoxifying enzymes clustered with the P450 system must be overcome. Thus, S-metabolism competes ineffectively with target DNA for reactive vinyl chloride (VC) metabolites, epoxide hydrolase is important to the metabolism and carcinogenicity of alfatoxins and polycyclic aromatic hydrocarbons (benzo[a]pyrene, etc.), and the non-toxic 2-naphthylhydroxylamine N-glucuronide acts as a transport form in 2-naphthylamine bladder cancer. VC liver-cancer pathogenesis is explicable in terms of the presence of the glutathione S-transferase detoxifying system in hepatocytes and its absence from the fibroblastic elements, and of the VC concentrations reaching the liver by different administrative routes. In VC carcinogenicity, chemical reactions give imidazo-cyclization products with nucleoside residues of target DNA, and in benzene leukaemia, Z,Z-muconaldehyde forms cyclic products containing a pyrrole residue linked to purine. Increased HbCO concentrations reduce the O2-carrying capacity of the blood, and the changed shape of the O2-Hb dissociation curve parallels disturbance in O2 unloading. CN- acts on electron transport and paralyses respiration. In telodrin poisoning, preconvulsive glutamine formation abstracts tricarboxylic acid intermediates incommensurately with normal cerebral respiration. Antigen-antibody complexing depletes the antibody titre, available against infection. At high doses of Cd, Cd-thionein filtered through the kidneys is reabsorbed and tubular lesions produced. Some organophosphate insecticides promote irreversible acetylcholinesterase phosphorylation and blockade nerve function, and others react with neurotoxic esterase to cause delayed neuropathy. The evidence for Paraquat pulmonary poisoning suggests a radical mechanism involving three interrelated cyclic reaction stages. The action of N- and O8 (O substituent in 6-position of the purine) demethylases explains deletion mechanisms for DNA-alkyl adducts. DNA-directed synthesis in the presence of ultimate carcinogens provides for an estimation of misincorporations, which implicate the same transversions as those found by direct mutagenicity testing. Chemical carcinogens recognize tissue-sensitive cells and modify their heritable genetic complement. Oncoproteins encoded by activated oncogenes signal the transformation of normal cells into cancer cells. The importance of the H-ras oncogene and p53 tumour-suppressor gene is stressed. Antidotal action is analysed; for example, parenteral glutamine administration to telodrin-intoxicated rats restores the depleted cerebral glutamate level and prevents seizures. Glutamate acts as anticonvulsant in petit mal epilepsy. In general, therefore, the reaction of the toxicant-related substance with the relevant target-tissue macromolecule accounts for the biochemical/biological events at a cellular level a

N-Dephenylation of N-phenyl-2-naphthylamine (PBNA) is strictly limited in dogs, and a 5 mg/kg dose gives 0-10 microng of urinary 2-naphthylamine (BNA), which does not appear to undergo further metabolism. Neither 2-naphthylhydroxylamine (BNHA) nor 2-amino-1-naphthylsulphate were detected in the urine of treated animals. Urinary output of BNA varies markedly between dogs, and at different times in the same animal. The extent of PBNA N-dephenylation is unaltered by chronic administration. Calculations based on Druckery and Küpfmüller's equation (1948) and present data indicate that, for dogs to form BNA tumours through exposure to a relatively high dose-level of PBNA, the period of daily dosing would occupy, or even exceed, the normal life-span. The carcinogenic risk of PBNA to human subjects is discussed.

N-Phenyl-2-naphthylamine has been synthesized (1) with 14C in positions 1, 4, 5 and 8, (2) with 13C in position 8 (small amounts of [1-13C] naphthalene and 2-[8-13C]naphthylamine are formed as by-products), and (3) with the N-phenyl nucleus uniformly labelled with 14C.

14C02 output from carboxy-14C-labelled aliphatic carboxylic acids is measured in the micro-scale Kolbe reaction. Irrespective of whether rats were dosed with 1,1-dichloro[1-14C]ethylene or with chloro[1-14C]acetic acid, 1 mol.equiv. of the resulting thio[14C]diglycollic acid yields by electrolysis approx. 0.7 equiv. of 14CO2, which is interpreted in terms of the labelling of one of the carboxylic acid groups of thiodiglycollic acid. This observation provides important evidence concerning thiodiglycollic acid biosynthesis from 1.1-dichloroethylene.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 80 years the Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

Up to 88% of a single dose of methyl[14C]methacrylate in rats is expired as 14CO2 in 10 days (65% in 2 h), irrespective of the route of administration and of the specific labelling of the propylene residue of the molecule. The implications of this observation, and of the excretion of small amounts of [14C]methylmalonate, [14C]-succinate and probably of [14C]beta-hydroxyisobutyrate and 2-formylpropionate, and of the formation of [14C] normal, physiological metabolites that may be accounted for by anabolism both from 14CO2 and from [14C]acetate emergent from the citric acid cycle, are that the metabolic pathway concerned involves intermediary metabolism and relates to mitochondrial function. Present findings are discussed in relation to the imputations of a report of carcinogenic risk.