Klimacharakter und Pflanzendecke

Ohne Zusammenfassung     

4-Nitroquinoline-1-oxide: factors determining its mutagenicity in bacteria

In bacteria, 4-nitroquinoline-1-oxide (NQO) causes primarily mutations of the base-substitution type although frameshift mutations are also induced. The adducts formed are presumably recognized by error-prone DNA repair enzymes as evidenced by the much greater activity in plasmid pKM101-bearing tester strains. Although reduction of the nitro group appears to be required for mutagenic activity, this reduction is not catalyzed by the nitroreductase required for the demonstration of the mutagenicity in bacteria of other nitro-containing mutagens (nitrofurans, 2-nitronaphthalene, nitrofluorenes). The reduction of the nitro group appears to be catalyzed by a different nitroreductase. The mutagenicity of the non-carcinogenic 3-methyl-4-nitroquinoline-1-oxide (meNQO) may be related to this newly recognized nitroreductase. It is proposed, further, that the ultimate mutagenic intermediates derived from NQO and MeNQO differ.     

The influence of the proportion of carcinogens on the cost-effectiveness of short-term tests

The cost-effectiveness of using short-term genotoxicity tests to screen unknown chemicals for carcinogenicity depends upon the inherent reliability of the tests (sensitivity, or fraction of carcinogens giving positive results, and specificity, or fraction of non-carcinogens giving negative results) and also upon the proportion of carcinogens in the population of chemicals to be screened. Individual tests may be combined into batteries to improve reliability; however, this requires decision rules to declare the overall result positive or negative. A framework for developing such rules based upon minimizing costs of false-positives and false-negatives was presented in a seminal paper by Lave and Omenn (1986, Nature (London), 324, 29-34). We have extended their work, which is based on logit analysis, to consider, using Bayes' theorem, the influence of the proportion of carcinogens upon the decision rules for declaring a battery result positive or negative. If the proportion of carcinogens is high (20% or greater), then the most effective tests are those with high sensitivity, and if the proportion of carcinogens is low, then the most effective tests are those with high specificity.     

A pharmacological comparison of [3H]GBR12935 binding to rodent striatal and kidney homogenates: binding to dopamine transporters?

Binding of [3H]GBR12935 to homogenates of mouse and rat striatum and kidney was studied. [3H]GBR12935 bound to both tissue preparations with high affinity (mouse striatum Kd = 2.4 +/- 0.4 nM, n = 4; mouse kidney Kd = 3.8 +/- 0.9 nM, n = 4), in a saturable (striatal Bmax = 1.5 +/- 0.4 pmol/mg protein; kidney Bmax = 4.9 +/- 0.5 pmol/mg protein) and reversible manner. Saturation experiments revealed the presence of a single class of high affinity binding sites in both tissues of both species. Mouse kidney appeared to possess a greater density of [3H]GBR12935 binding sites than the striatum while the reverse situation prevailed for the rat. Although two dopamine uptake inhibitors, namely GBR12909 and benztropine, displaced [3H]GBR12935 binding from striatal and kidney homogenates with a similar affinity in both tissues of these species, unlabelled mazindol, (+/-)cocaine, nomifensine and amfonelic acid were significantly (P < 0.001-0.02) more potent inhibitors of [3H]GBR12935 binding in the striatum than in the kidney. While the pharmacological profile of [3H]GBR12935 binding in the rodent striatum compared well with that of the dopamine transporter reported previously, the pharmacology in the kidney was considerably different to that in the striatum. GBR12909 (1-30 mg/kg, i.p.), a close analog of GBR12935, induced significant antidiuretic and antinatriuretic effects in spontaneously hypertensive rats. These data suggest that while [3H]GBR12935 labels the dopamine uptake sites in the brain, it does not appear to label similar sites in the kidney. The mechanism of action of GBR12909 on sodium and water excretion remains to be determined.     

Mutagenicity of nitropyrenes for Escherichia coli: requirement for increased cellular permeability

Nitropyrenes are mutagenic to E. coli strains that have increased permeabilities to large molecules and carry plasmid pKM101.     

Carcinogenic N-hydroxylaminopurine derivatives do not act as base analog mutagens in Salmonella typhimurium

N-Hydroxylaminopurines are highly mutagenic for growing as well as resting Salmonella typhimurium strain TA100 and to a lesser extent for strain TA98. Aminopurines, under similar conditions, are not mutagenic. N-Methylhydroxylaminopurine, under similar conditions, exhibits only minimal activity. The results are taken to indicate that unlike non-hydroxylated aminopurines, N-hydroxylaminopurines exert their mutagenicity not by acting as base analogs but by direct covalent binding with DNA-guanine.     

On global stability of discrete population models

A necessary and sufficient condition for the global stability of a large class of discrete population models is provided which does not require the construction of a Liapunov function. The general result is applied to difference equations defined in terms of “two hump” functions and to an example of frequency dependent selection.