Genotype-specific reduction in methyl nitrosourea (MNU) induced sister chromatid exchanges (SCE) in vivo during aging

Summary We studied mice from five strains (BALB/c, C3H/HeSnJ, C57BL/6J, Cs^b and 129/ReJ) at two ages (young, 10±1 weeks; and old, 67±3 weeks) for the induction of sister chromatid exchanges (SCEs) in vivo by methyl nitrosourea (MNU). The SCE frequency is genotype-specific. The F₁ phenotype resembles the low responding parent. SCE induction is significantly lower in the older animals of each strain than their younger counterparts, and the reduction of SCE/cell with old age is strain-specific. A general explanation for these results must include strain differences in relative mutagenic sensitivity, genotype-specific pattern of reduction in DNA repair and other such factors affecting SCE formation, with old age.     

Immunostimulating lipopeptide,LtriP (RP 56142): Comparison of the effect on hepatic cytochrome P 450 modulation and radioprotection in male and female of three mouse strains

The sex-dependent effect of lauroyl-L-Ala-D--Glu-L,L-A₂pmNH₂ (LtriP, RP 56142) on hepatic microsomal cytochromes P 450 (cyt P 450) was studied in three mouse strains NMRI, C3H/OuJ and C3H/HeJ. In NMRI and C3H/OuJ, strains which are responsive to bacterial lipopolysaccharides (LPS-responsive), regardless of the sex of the mouse, significant decrease in the amount of cyt P 450 was observed after LtriP treatment, with a concomitant reduction in ethoxyresorufin-O-deethylase (cyt P 450 1A-dependent) and 7-ethoxycoumarin-O-deethylase activities. This was not seen in C3H/HeJ (LPS-hyporesponsive) mice. These effects may be related to LtriP-dependent cytokine induction, since neither LtriP nor LPS stimulated interleukin-1 (IL-1) secretion by C3H/HeJ macrophages. 11- and 12-hydroxylations (11- and 12-OH) of lauric acid were compared in C3H/OuJ and C3H/HeJ mice. LtriP depressed the total enzymatic conversion of lauric acid in the two strains without modification of the 11/12-OH ratio for C3H/OuJ or male C3H/HeJ mice. However, in females C3H/HeJ mice this decrease was particularly significant and concerned especially the 12-OH activity (a marker of cyt P450 4A family). Although males of the three strains were more sensitive to irradiation than females, LtriP exerted a sex-independent radioprotection on NMRI and C3H/OuJ mice. Its radioprotective effect was illustrated by the preservation of all the enzymatic activities studied in treated NMRI mice, contrary to irradiated control animals. In contrast, for the C3H/HeJ strain, males were not protected by LtriP treatment and, furthermore, females showed a marked sensitization to irradiation.The effects in CH3/HeJ strain implicate LtriP in the control of cyt P 450 induction and of sensitivity to irradiation independently of IL-1 induction.     

A morphometric study of spermatogenesis in the testes of mice of a senescence accelerated strain

The morphometric parameters of spermatogenic cells in a mouse strain prone to accelerated senescence (SAM-P), a novel murine model of spontaneously promoted aging, were compared with those of a SAM resistant strain (SAM-R) after birth until 40 weeks (mean life span of SAM-P). A mixture of gonocytes and spermatogonia were present in the testis in 1-week-old mice, and no gonocytes were observed in 2-week-old mice. At 6 weeks of age, the absolute number of spermatogonia in SAM-P was 27% greater than that in SAM-R, whereas the cell number in 40-week-old SAM-P was 17% less than in SAM-R. Primary spermatocytes were first observed in 3-week-old animals, and the cell numbers in SAM-P at 3, 5 and 6 weeks were 78%, 31% and 25%, respectively, greater than in SAM-R, whereas the cell number in SAM-P at 40 weeks was 30% less than SAM-R. Round spermatids were first observed in all SAM-P at 4 weeks old, but 20% of SAM-r had no spermatids and the rest had only a few. At 5 and 6 weeks old, the absolute numbers of round spermatids in SAM-P was about 34% and 41%, respectively, greater than in SAM-R, whereas the cell number in 40-week-old SAM-P was about 34% less than SAM-R. These results indicate that testicular maturation begins at an earlier age in SAM-P than SAM-R. Furthermore, at the age of 40 weeks signs of testicular deterioration are evident in SAM-P mice only     

Steroid hormones enhanced sister-chromatid exchange in cultured CHO cells

Summary The influence of steroid hormones on the induction of sister-chromatid exchange (SCE) in cultured CHO cells was studied. It was observed that estradiol-17 , estriol, estrone and ethynyl estradiol treatments enhanced SCE rates compared to the controls. Overall, these compounds produced a dose response effect. The importance of a detailed study on the long-term genetic effects of steroids on mammalian cells is emphasized.This work was supported by NIH-Minority Biomedical Research Support Program (MBRS), Grant No. RR 08124-11. The author is thankful for the technical assistance provided by NIH-MBRS student, Hoang Duong.     

Decreased incidence of renal cell carcinoma in rats with one kidney ingesting N-4-(4'-fluorobiphenyl)acetamide.

Buffalo strain male rats, 12 weeks of age, ingesting 0.04% N-4-(4'-fluorobiphenyl)acetamide in a semisynthetic diet with both kidneys intact were more susceptible to the development of hyperplasia and carcinomas of the kidney than were rats with a uninephrectomy.     

Identification of calcium antagonist receptor binding sites using (3H)nitrendipine in bovine tracheal smooth muscle membranes

(3H)Nitrendipine binding to the bovine tracheal muscle membrane at 25 degrees C was rapid, saturable (Bmax = 14.8 +/- 3.9 fmol/mg protein) and of high affinity (Kd = 0.15 +/- 0.04 nM). The rank order of Ca2+ antagonists competing for airway (3H)nitrendipine binding was nitrendipine not equal to nisoldipine not equal to nifedipine much greater than verapamil. Cromolyn, however, neither inhibited nor increased the binding.     

Sterilization by irradiation of Cadra coutella (Wlk.) (Lepidoptera, Pyralidae) males increased by female sex pheromone

Sterilization by irradiation was studied in 0-24 hour old males of Cadra cautella (Ephestia cautella) exposed to 40 Krad of gamma radiation from a 60 cobalt source at a rate of 2250-2200 rad/minute in the presence of female sex pheromone. This radiation dose failed to induce the desired degree of sterility in the absence of pheromone. Pheromone was extraced from the virgin females and applied to filter paper at doses of .1, .5, and 1 female equivalent which was then introduced into containers containing 15-18 males 3 minutes prior to irradiation. Excitation and increased activity of the insects was observed when compared to the controls without the pheromone. The proportion of low percentage hatch increased with increased pheromone presence. The difference between absence and presence of pheromone was marked. It is concluded that these results are evidence of the value of this approach of preconditioning to irradiation when induction of sterility is the objective.     

Alpha 1-adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

The effect of norepinephrine on fatty acid synthesis (3H2O incorporation into fatty acids), on fatty acid oxidation to CO2 and on ketogenesis was studied in isolated hepatocytes of fed rats. After incubation with norepinephrine (50 microM), lipogenesis was lower (5.7 +/- 1.1 nmoles 3H2O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5 +/- 1.7; n = 6, p less than 0.02). In contrast, (1-14C) palmitate conversion into total ketone bodies was increased to 10.9 +/- 1.8 nmoles/mg/30 min with norepinephrine, vs 8.5 +/- 1.6 in controls (p less than 0.05), and more (1-14C) palmitate was converted to 14CO2 with norepinephrine than in controls (1.48 +/- 0.10 nmoles/mg/30 min vs 1.06 +/- 0.11, p less than 0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the alpha 1-receptor blocker prazosin, but not by alpha 2 or beta-blockers. The results demonstrate that the ketogenic effect of norepinephrine is coupled with an inhibitory effect on lipogenesis which may be explained by diminished activity of acetyl-CoA carboxylase, diminished formation of malonyl-CoA and decreased activity of carnitine palmitoyl transferase I.     

Prevention of enteral radiocesium absorption by hexacyanoferrates(II) in piglets

The efficacy of different hexacyanoferrates(II) in preventing the enteral absorption of 134Cs was studied in piglets. As compared to the controls, oral application of 134Cs together with KFe[Fe(CN)6], NH4Fe[Fe(CN)6], or Fe4[Fe(CN)6]3 resulted in a strong reduction of the 134 Cs-uptake by more than 97%. The decrease in enteral absorption depends on the dose of administered hexacyanoferrate(II), whereas differences between the compounds under study were small. The biological half-life of 134Cs in non-hexacyanoferrate(II) treated piglets was 21.6 +/- 3.3 days (mean +/- SD).     

Age distribution of circulating alpha-interferon

A sensitive radioimmunoassay showed that circulating alpha-interferon in the plasma of healthy individuals was low in children and reached the highest level in the young adult, then declined gradually with age. Circulating alpha-interferon was 0.201 +/- 0.059 ng/ml in males (n = 19) and 0.184 +/- 0.076 ng/ml in females (n = 14) at ages 30-39 years old. It was noted that circulating alpha-interferon was maintained up to a certain level even in elderly individuals.     

Response of the brown trout (Salmo trutta, L. 1766) and rainbow trout (Salmo gairdneri Richardson, 1836) to infection by a new rhabdovirus]

Intra peritoneal injection of 200 g Trout hold at + 12 degrees C with 2x10(8) p.f.u. of a new Rhabdovirus (strain 23.75) induces an interferon synthesis within 2 days. (IF titres reaching 2,000 units/ml). 1 month later, the surviving Fish exhibit a specific anti 23.75 neutralizing serum activity (titre 40 to 80) which has been demonstrated to be due to immunoglobulins. This seroneutralization is also recorded in 1/3 of the survivors of natural infection.     

Hemolymph proteins in an ascitic condition,induced by lethal1(3)gl tumorous tissue inDrosophila hydei

Summary Drosophila hydei larvae homozygous for the gene1(3)gl may survive to the age of 3 weeks, become bloated and be incapable of metamorphosis. Wild-type flies after the injection of a fragment of the1(3)gl disc, which has been previously culture in vivo for 40–500 days, also become bloated (ascitic reaction). In the hemolymph of both the advanced1(3)gl larvae and ascitic adult hosts the accumulation of a specific protein is observed.Acknowledgments. This work was supported by the Swiss National Science Foundation under Grant No.3.792-0.76 and the Georges und Antoine Claraz-Schenkung. We thank Prof. H. Gloor, University of Geneva, and Prof. P.S. Chen, University of Zürich, for advice and criticism.     

Half-life of dehydroepiandrosterone sulfate (DHAS) during pregnancy]

During pregnancy the half-life of DHAS was measured after non tritiated DHAS infusion. At 30 weeks, the mean value obtained for DHAS half-life was 3.64 h +/- 0.74 and it was 3.67h +/- 0.38 at 38 weeks. The half-life of DHAS is shorter in pregnant than in non-pregnant women. Among 14 pathological pregnancies that we studied, 13 cases exhibited a DHAS half-life significantly longer than the average value obtained in normal pregnancies. In retarded fetal growth, the half-life of DHAS was more closely related to fetal than to placental weight.     

Sister chromatid exchanges in lymphocytes of normal and alcoholic subjects.

The effects of alcohol consumption, cigarette smoking and age on sister chromatid exchange (SCE) frequency in human lymphocytes were assessed by means of multiple linear regression. An increase in SCE rates was associated with alcohol consumption (p = 0.0001), smoking (p = 0.0231), and, to a small extent (p = 0.057), age. These three confounding factors explain 48% of the inter-personal variation in SCE rates among subjects studied.     

Plasmids controlling the resistance to several antibiotics in C. perfringens type A, strain 659]

A strain of C. perfringens type A, isolated from a patient, was found to be resistant to four antibiotics: tetracycline (Tet), chloramphénicol (Chl), erythromycin (Ero) and clindamycin (Cli). Clones resistant to only two drugs (Tet-Chl or Ero-Cli), or sensitive to all drugs were found in cultures of the wild-type strain treated by acridine dyes or ethidium bromide. DNA analysis by equilibrium centrifugation confirmed that the original strain contains two resistance plasmids, one called Rip 401 (Tet-Chl) and the other Rip 402 (Ero-Cli), which represent respectively 1.8 +/- 0.2% and 2.3 +/- 0.2% of the total amount of DNA in this strain of Cl. perfrigens.     

Sister chromatid exchanges in lymphocytes of normal and alcoholic subjects

The effects of alcohol consumption, cigarette smoking and age on sister chromatid exchangen (SCE) frequency in human lymphocytes were assessed by means of multiple linear regression. An increase in SCE rates was associated with alcohol consumption (p=0.0001), smoking (p=0.0231), and, to a small extent (p=0.057), age. These three confounding factors explain 48% of the inter-personal variation in SCE rates among subjects studied.We are grateful to Dr D. Krapavickaité for performing, the statistical analysis, and to Mrs V. Navickiené for technical assistance. We also wish to thank Dr B. Lambert (Stockholm, Sweden) for his valuable suggestions.     

Oyster mushroom (Pleurotus ostreatus) reduces the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat liver microsomes

The effect of dried oyster mushroom (Pleurotus ostreatus) on cholesterol (C) content in serum, in lipoproteins and in liver, and on the activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in liver microsomes, was studied in male rats (strain Wistar, initial body weight 75 g) fed on low-cholesterol (9 mg/100 g) and high-cholesterol (0.3%) diets. Addition of 5% oyster mushroom to both diets reduced significantly the C-content in serum (by 30%), in very-low- and low-density lipoproteins (in a 11 ratio to the decrease of total serum C) and in liver (by 50%), as well as the activity of HMG-CoA reductase (by more than 30%).     

Steroid hormones enhanced sister-chromatid exchange in cultured CHO cells

The influence of steroid hormones on the induction of sister-chromatid exchange (SCE) in cultured CHO cells was studied. It was observed that estradiol-17 beta, estriol, estrone and ethynyl estradiol treatments enhanced SCE rates compared to the controls. Overall, these compounds produced a dose response effect. The importance of a detailed study on the long-term genetic effects of steroids on mammalian cells is emphasized.     

Evidence of a direct action of triiodothyronine (T3) on the cell membrane of GH3 cells: an electrophysiological approach

Electrophysiological experiments demonstrate that triiodothyronine (T3) exerts a direct effect on the membrane of a strain of cultured rat pituitary tumor cells, GH3/B6. These cells respond to pressure application of T3 (2-5 nl, concentration 1 X 10(-10) M) with an increase in the membrane resistance (Rm) and a hyperpolarization. Spontaneously firing cells become silent.