Some problems of spontaneous and induced mutagenesis in mammals and man.

The culture time of rabbit lymphocytes (41–42 h) that provides cells in their first post-stimulation mitosis, was estimated on the basis of the mitotic index, dicentric yield and presence of the cells with these aberrations unaccompanied by acentric fragments, studied as a function of culture duration. The cells obtained in metaphase from cultures terminated at this time displayed no donor-to-donor variation where induction of dicentrics by X-rays was concerned.Rabbit venous blood was irradiated in vitro with a range of X- and gamma-ray doses, and dose-effect curves were obtained by regression analysis. Sixteen rabbits were irradiated in vivo (uniform whole-body irradiation), and blood was sampled 10 min, 6, 24, and 48 h after exposure. The frequency of dicentrics in the lymphocytes cultured did not change significantly over the first 24 h after irradiation. Dose-effect relationships in vivo fell within one standard error confidence limits of the respective curves in vitro. The authors conclude that the latter may be used for estimation of dose in vivo under conditions of homogeneous whole-body irradiation.     

Sources of spontaneous mutagenesis in bacteria

Mutations in an organism’s genome can arise spontaneously, that is, in the absence of exogenous stress and prior to selection. Mutations are often neutral or deleterious to individual fitness but can also provide genetic diversity driving evolution. Mutagenesis in bacteria contributes to the already serious and growing problem of antibiotic resistance. However, the negative impacts of spontaneous mutagenesis on human health are not limited to bacterial antibiotic resistance. Spontaneous mutations also underlie tumorigenesis and evolution of drug resistance. To better understand the causes of genetic change and how they may be manipulated in order to curb antibiotic resistance or the development of cancer, we must acquire a mechanistic understanding of the major sources of mutagenesis. Bacterial systems are particularly well-suited to studying mutagenesis because of their fast growth rate and the panoply of available experimental tools, but efforts to understand mutagenic mechanisms can be complicated by the experimental system employed. Here, we review our current understanding of mutagenic mechanisms in bacteria and describe the methods used to study mutagenesis in bacterial systems.     

Distribution of enterobacteria in man and small mammals

The species composition of the most common enterobacteria isolated from the intestine of 825 patients with intestinal dysbacteriosis and 292 small mammals of different species is compared.     

Humoral and neurogenic factors in two-kidney renovascular hypertension

A "bolus" dose (110 microgram) of the angiotesin II (A II)-blocker 1-Sar-8-Ala-A II (Saralasin, S) followed by its slow rate infusion (5 microgram/min/rat) for thirty min, was injected before and after the complete ganglionic blockade by pentolinium (P) in unanaesthetized unilaterally clipped renal hypertensive rats (the opposite kidney remained untouched). Pentolinium was also injected like a "bolus" dose (3 mg) followed by slow infusion (0.1 mg/min/rat) for thirty min. The observations were made until the fifth week after clipping the left renal artery. A consistent maximal hypotensive response was observed after the "bolus test" with both drugs. When S was the first drug injected, an inverse correlation was found between the percent decrease in arterial pressure (BP) by S and the percent decrease in BP by P (r = --0.83, P < 0.01, n = 8). Thus whenever a greater hypotensive effect was obtained by S, a smaller neural pressor component remained to be blocked by P. On the other hand, when P was the first drug injected a lesser A II pressor component remained to be blocked by S in the hypertensive rats. The results suggest that a considerable A II pressor effect in two-kidney renovascular hypertension is mediated via neurogenic mechanisms from the first week. A direct pressor vasoconstriction was found to be significant in cases with very high plasma-renin activity.     

On spontaneous mutagenesis and cell cultivation conditions.

The leu2 revertant content of a Saccharomyces cerevisiae cell culture increases as the leucine concentration in the nutrient solid medium decreases. Reversions form in the S-phase of the cell cycle. If a cell culture from a medium with a low concentration of leucine containing the revertants which have just formed is transferred on a medium with a normal or higher than normal leucine content, these 'newborn' revertants disappear at the end of the G1-phase or at the beginning of the S-phase of the next cell cycle. These data can be explained either by a difference in the ability of revertants formed in the culture to compete with the cells of the initial strain on different media, or on the basis of the intermediate heteroduplex model proposed by F.W. Stahl (1988).     

Effect of gossypol on spermatogenesis and fertility in man and mammals

This review summarizes the main results of experimental and clinical studies of a new antifertile agent, gossypol, a polyphenolic compound isolated from the cotton. This compound disturb the normal course of spermatogenesis and affects, first of all, the locomotory system of mature spermatozoa of the man and some mammal species. The mechanism of gossypol action on the development of germ cells is discussed. Since the action of gossypol is reversible and it does not induce strong side effects, the possibility of its application for the control of birth rate is considered.     

Humoral factors of transplantation immunity in carp]

The levels of isohemagglutinins, isohemolysins, heterohemagglutinins and lysozyme in blood serum of one and half year old carps have been fixed after scales transplantation. Since three weeks after grafting isohemagglutinins and isohemolysins were revealed in recipient fishes with the prevalence of 25% and 95% respectively. Intact carps from the same group were lack of these antibodies. Recipient and intact fishes did not differ reliably by heterohemagglutinins and lysozyme level in the blood serum. There was no correlation between destroyed allografts share and hemolysins titre of serum, so the double role of humoral antibodies in grafting immunity in carps can be assumed.     

Studies in symbiosis: hair follicle mites of mammals and man

A programme of study using hair follicle mites of man, dog, and other mammals is presented which has been successful in stimulating student interest in symbiosis. Brief background information on these mites, with illustrations, is provided as well as details of laboratory procedures for secondary school through college level classes. Suggestions for more advanced or independent studies using these mites are also made so that exceptional, career-oriented students and their teachers can explore adaptations to symbiosis in depth.     

Roles of RecA protein in spontaneous mutagenesis in Escherichia coli

To verify the extent of contribution of spontaneous DNA lesions to spontaneous mutagenesis, we have developed a new genetic system to examine simultaneously both forward mutations and recombination events occurring within about 600 base pairs of a transgenic rpsL target sequence located on Escherichia coli chromosome. In a wild-type strain, the recombination events were occurring at a frequency comparable to that of point mutations within the rpsL sequence. When the cells were UV-irradiated, the recombination events were induced much more sharply than point mutations. In a recA null mutant, no recombination event was observed. These data suggest that the blockage of DNA replication, probably caused by spontaneous DNA lesions, occurs often in normally growing E. coli cells and is mainly processed by cellular functions requiring the RecA protein. However, the recA mutant strain showed elevated frequencies of single-base frameshifts and large deletions, implying a novel mutator action of this strain. A similar mutator action of the recA mutant was also observed with a plasmid-based rpsL mutation assay. Therefore, if the recombinogenic problems in DNA replication are not properly processed by the RecA function, these would be a potential source for mutagenesis leading to single-base frameshift and large deletion in E. coli. Furthermore, the single-base frameshifts induced in the recA-deficient cells appeared to be efficiently suppressed by the mutS-dependent mismatch repair system. Thus, it seems likely that the single-base frameshifts are derived from slippage errors that are not directly caused by DNA lesions but made indirectly during some kind of error-prone DNA synthesis in the recA mutant cells.     

Molecular mechanisms for controlling spontaneous and induced mutagenesis.

Errors in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. We also deal with suppression of alkylation-induced mutations by O6-methylguanine-DNA methyltransferase.