Epidemiology and the identification of metals as human carcinogens.

Classification of substances as probable human carcinogens under the current IARC classification scheme is dependent on epidemiological evidence. The epidemiological data relating to the four metals currently identified as probable human carcinogens, in the metallic form or in the compounds, are reviewed and the weaknesses identified. These weaknesses lie mainly in exposure assessment. The weaknesses may be overcome to some extent by the use of metademographic methods as applied recently to the respiratory cancers that occurred at the Clydach Nickel Refinery in the first 30 years of this century. The general conclusion is that the epidemiological data relating to metals are unsatisfactory bases for the IARC classifications. There is a need to revise these classifications and to make them more precise by identifying exactly the substances which have caused human cancers.

Analysis of nickel refinery dusts.

After characterization of bulk samples by inductively coupled plasma emission spectroscopic (ICP-ES) quantitative analysis and X-ray powder diffraction studies, single particle techniques using quantitative image analysis, scanning electron microscopy--energy dispersive analysis by X-ray, and finally laser beam ionization mass spectrometry analysis (LIMA) for surface analysis have been applied to historical nickel refinery dust samples from the nickel refining plant at Clydach in Wales. There were two historical samples of processed material from 1920 and 1929. These samples had a remarkably small particle size range, mean 3 microns and range, 0.75-24 microns. The most significant difference in elemental composition was the presence of 10% arsenic in the 1920 sample compared with 1% in the 1929 sample. The X-ray spectra revealed the presence of NiO in both. However, surprisingly, CuO was identified only in the 1929 sample. Of particular interest was the presence of a component, in the 1920 sample only, identified as the mineral orcelite, a copper-iron-nickel-arsenide-sulphide mineral, predominantly, Ni5-XAs2. Using the LIMA technique, it was found that in both samples, arsenic and arsenic derivative peaks are prominent, indicating the surface availability of arsenic compounds.

The use of primuline to identify the septum polysaccharide of the fission yeast Schizosaccharomyces pombe.

Treatment of cells and purified cell walls of the fission yeast Schizosaccharomyces pombe with primuline reveals the septum as a bright fluorescent band. When polysaccharides containing (1----3)-beta-, (1----6)-beta- or (1----3)-alpha-glucosidic linkages are treated with primuline, only those molecules containing chains of (1----3)-beta-glucosyl residues are stained. This implies that (1----3)-beta-glucan is present in the septum of Schiz. pombe as the main constituent.

Magnesium ions and the control of the cell cycle in yeast.

A study has been made of the role of magnesium ions in cell division cycle control in the fission yeast, Schizosaccharomyces pombe, and the budding yeast, Kluyveromyces fraglis. Synchronization of cell division in these organismms can be induced by restoring magnesium to magnesium-exhausted cultures. In S. pombe, a correlation exists between the time taken for cells to enter the first synchronous division and the period of magnesium exhaustion. During short-term incubation in magnesium-deficient media, S. pombe cells are observed to continue growth in length, but they fail to make a cell plate and divide; long-term magnesium deficiency results in the production of aberrant cell forms, and a reduction in viability. Analysis of total cell magnesium in cultures of both S. pombe and K. fragilis, synchronized by various induction and selection procedures, revealed that there is a fairly steady fall in magnesium concentration as cells grow, terminating in a rapid influx of magnesium just before cell division. This leads to the hypothesis that falling magnesium concentration may act as a transducer of cell size, eventually triggering spindle formation and a membrane change which permits rapid uptake of magnesium to a concentration which brings about spindle breakdown. The hypothesis was tested directly using the divalent cation ionophore, A23187, in the absence of calcium ions; the results obtained showed that a short pulse of A23187, very late in the cell cycle, accelerated cells into division and shortened the subsequent cycle. The hypothesis is discussed in relation to current models of cell cycle regulation.

Histone-like protein fractions of Kluyveromyces fragilis and their relation to the cell cycle.

Protein fractions were obtained from Kluyveromyces fragilis by pH titration, a technique used for histone extraction, following the inclusion of a distilled water extraction stage, and the fractions partially characterized. The inclusion of a distilled water step resulted in a tenfold purification of the fraction obtained at pH 2.20 as compared with pH titration alone. In synchronous cultures induced with 2'-deoxyadenosine or prepared by selection this fraction displayed a stepwise accumulation, and doubled in quantity at a point about one third of a cycle after cell division. The fraction obtained at pH 1.35 resembled calf thymus f2a2 histone in its extraction properties and amino acid composition, and also showed a possible stepwise accumulation. Other fractions appear to accumulate exponentially.

2'-Deoxyadenosine and A23187 as agents for inducing synchrony in the budding yeast, Kluyveromyces fragilis.

The effects of induction synchrony by 2'-deoxyadenosine and the ionophore A23187 were compared with selection synchrony methods in Kluyveromyces fragilis. 2'-Deoxyadenosine synchronizes nuclear division and this is followed by synchronous cell division, but DNA synthesis is not synchronized. The ionophore A23187 also induces synchronous nuclear division and synchronous cell division, but likewise does not synchronize DNA synthesis.