Resistance of Drosophila to cadmium: biochemical factors in resistant and sensitive strains.

With regard to cadmium toxicity, Drosophila strains v;bw and Austin represent extremes in resistance and sensitivity, respectively. Both strains produced metallothionein (MT) in response to Cd ions in their diet. Austin produced more metallothionein than v;bw at Cd ion levels below 0.2 mM, when both strains were allowed lifetime development on Cd2+-containing media. When the rate of MT appearance was measured for 4 days in young adults the results showed no clear trend with time within a strain or between strains. The plot of LC50 vs. MT levels for identical developmental conditions revealed that for v;bw small increases in MT corresponded to large increases in resistance whereas for the sensitive Austin even large increases in MT had comparatively little effect on increasing LC50. Results given here suggest that differences in total MT content do not explain the genetically demonstrable difference in Cd2+-resistance between v;bw and Austin. However, since two MT genes are identified in Drosophila, differences in resistance could be reflective of greater relative amounts of one "more important" MT in the resistant fly.

Strontium toxicity in Drosophila melanogaster.

The Drosophila strains v;bw and Austin represent the extremes in resistance and sensitivity, respectively, to the toxic effects of CdCl2 in the diet. Using the six genotypes containing the possible combinations of the three main chromosomes for v;bw and Austin, we had shown previously that the gene(s) for cadmium resistance is on the X-chromosome. In this paper it is shown, using the same six genotypes, that the gene(s) for strontium resistance is on the second chromosome, as measured by LC50 values.

Inorganic concepts relevant to metal binding, activity, and toxicity in a biological system.

Selected physical and inorganic concepts and factors which might be important in assessing and/or understanding the fate and disposition of metal compounds in a biological environment are reviewed. The stereochemistry (geometry), thermodynamic stability, redox properties, and intrinsic reactivity/lability are properties of metal compounds which can have a major influence on metal-target binding and on the eliciting of activity/toxicity. Concepts and factors are illustrated with appropriate examples where possible. Efforts to correlate the toxicity of metal compounds with a suitable indicator of toxicity should be expanded to include other parameters or combinations of parameters.

Correlations between pairs of simple physicochemical parameters of metal ions and acute toxicity in mice.

Our earlier study of correlations between single physical parameters characterizing divalent metal ions and their acute toxicity in mice is extended to linear combinations of pairs of parameters chosen from among the following five: ionic radius, sum of ionization potentials, atomic weight, Williams softness parameter, and electronegativity. Some improvements in the correlations are found by employing a two-parameter fit to a given set of toxicity data. Similar results are obtained when the grouping of metal ions is based on criteria suggested by Kaiser.

Ordering of metal-ion toxicities in different species--extrapolation to man.

Our previous attempts to predict the toxicities of 24 metal ions for a given species, using physicochemical parameters associated with the ions, are summarized. In our current attempt we have chosen indicators of toxicity for biological systems of increasing levels of complexity--starting with individual biological molecules and ascending to mice as representative of higher-order animals. The numerical values for these indicators have been normalized to a scale of 100 for Mg2+ (essentially nontoxic) and 0 for Cd2+ (very toxic). To give predicted toxicities to humans, extrapolations across biological species have been made for each of the metal ions considered. The predicted values are then compared with threshold limit values (TLV) from the literature. Both methods for predicting toxicities have their advantages and disadvantages, and both have limited success for metal ions. However, the second approach suggests that the TLV for Cu2+ should be lower than that currently recommended.

Resonance ionization spectroscopy for multiplex sequencing of tin-labeled DNA.

A method is described for synthesis of a tin reagent, triethylstannylpropanoic acid (TESPA), and its attachment to oligonucleotide primers. Except for the expected mobility retardation, the presence of [116Sn]-TESPA did not affect the sequencing ladder on electrophoresis gels. By using [120Sn]-TESPA and [35S]-dTTP simultaneously in the Sanger procedure, DNA bands on an electrophoresis gel were first located by autoradiography and then by resonance ionization spectroscopy to demonstrate the coincidence of the signals. Previous results using stable isotopes as labels on model compounds are now confirmed by their use in actual DNA sequencing products.