Activation of the carcinogen N-hydroxy-2-acetylaminofluorene by rat mammary peroxidase

Summary A peroxidase preparation from rat mammary gland parenchymal cells, a target tissue of arylamine carcinogens, was shown to activate the carcinogen N-hydroxy-2-acetylaminofluorene via a nitroxyl free radical intermediate to the more active carcinogens nitrosofluorene and N-acetoxy-2-acetylaminofluorene. Hydrogen peroxide, cumene hydroperoxide, and linoleic acid hydroperoxide were effective as substrates. The antioxidants ascorbate, propyl gallate and reduced glutathione prevented the free radical activation route.     

Activation of the carcinogen N-hydroxy-2-acetylaminofluorene by rat mammary peroxidase

A peroxidase preparation from rat mammary gland parenchymal cells, a target tissue of arylamine carcinogens, was shown to activate the carcinogen N-hydroxy-2-acetylaminofluorene via a nitroxyl free radical intermediate to the more active carcinogens nitrosofluorene and N-acetoxy-2-acetylaminofluorene. Hydrogen peroxide, cumene hydroperoxide, and linoleic acid hydroperoxide were effective as substrates. The antioxidants ascorbate, propyl gallate and reduced glutathione prevented the free radical activation route.     

Protection against mercuric chloride nephropathy by sodium selenite in the rat]

Daily intraperitoneal injection of 2.5 or 5 mumole HgCl2 to male Rats weighing 250 to 350 g induces an early intense increase of urine gamma-glutamyl transferase activity. In the same conditions, equimolecular administration of sodium selenite and mercuric chloride induces no increase of the enzymuria for the low dose: for the high dose- a minor and more persistent increase of urine GGT is observed. Thus, the activity of urines GGT allows, in vivo, to establish that sodium selenite protects Rat kidney against toxic effects of mercuric chloride.     

Pituitary-testicular relationships in the rat embryo]

LH given to the Rat embryo at the time of hypophysectomy by decapitation (18 days of intrauterine life) will prevent the drop in androgen synthesis which normally ensues. This is regarded as definite proof that androgen synthesis is under pituitary control in the rat embryo at late gestational stages. On the other hand, the decrease in androgen synthesis following testosterone injection to the pregnant female points to the fact that there is a negative feedback of testosterone on pituitary LH secretion.     

Activation by S-adenosylhomocysteine of norepinephrine and serotonin in vitro uptake in synaptosomal preparations from rat brain

Summary S-Adenosylhomocysteine (10^–7–10^–5 M) activated norepinephrine (NE) and serotonin (5HT) in vitro uptake in synaptosomal preparations from rat brain, but did not affect dopamine (DA) uptake. When administered to rats (7 mg/kg i.p.), it had the same effect on in vitro NE and 5HT uptake. It did not affect NE and 5HT release.Work achieved within the frame of the research contract institut Mérieux., Institut National des Sciences Appliquées.     

Stimulation of calcitonin secretion in the fasting newborn rat by ingestion of triglycerides]

The stomach gavage of fat (triglycerides) in the fasting newborn Rat induced a marked increase in the plasma concentration of immunoreactive calcitonin after 30 and 60 mn. Calcium chloride given by the same route at the dose of 20 mg calcium per kg body weight had a poor effect on calcitonin secretion. This stimulation was probably mediated through some gastro-intestinal hormone that has to be uncovered.     

Vitamin D3 sulfoconjugate distribution and evolution in pregnant or lactating rats]

24 hrs after intravenous injection of vitamin D3 35S sulfoconjugate the radioactivity in kidney is about twice as much in pregnant Rats as in lactating Rats. It decreases from 24 to 48 hrs in pregnant but increases in lactating Rats kidneys. Hydrolysis of vitamin 3H D3 sulfate is detected in kidney and liver extracts, the ratio of free vitamin D3 on vitamin D3 sulfate is higher in pregnant than in lactating animals. Mammary glands of lactating Rats contain mainly the unchanged vitamin D3 sulfate which can be hydrolysed by new born suckling pups.     

Serotonergic and cholinergic interaction in the regulation of pituitary-adrenal function in rats

It has been proposed that the central serotonergic inputs which modulate pituitary-adrenal secretion are mediated by cholinergic neurons. We have tested this hypothesis in intact rats. Male Sprague-Dawley rats were injected with cholinergic and serotonergic agents which enhanced transmitter function and with receptor blocking agents. Agents were injected, singly and in combination, into both unstressed and stressed animals. Since the response to cholinergic agents might be due to changes to vasopressin release, Brattleboro (vasopressin deficient) rats were also injected with cholinergic agents. The level of plasma corticosterone at 1-h post-injection was determined. Results indicate that the serotonin receptor blockade decreased the stimulatory, cholinergic effect of physostigmine. Cholinergic receptor blockers did not significantly reduce the corticosterone rise induced by 5-hydroxytryptophan. These results do not support the hypothesis of cholinergic mediation of serotonergic input. Nicotinic and muscarinic receptors appeared to exert opposing influences on the system. The nicotinic receptor antagonist was able to block the stimulatory effect of physostigmine. The muscarinic receptor antagonist significantly elevated plasma corticosterone levels. No differences were found in the effect of physostigmine on Brattleboro rats as compared to controls. These data are interpreted as suggesting that 1) the acetylcholine-induced stimulation of pituitary-adrenal function is mediated, in part, by serotonergic neurons; and 2) stimulation of nicotinic receptors is facilitatory whereas stimulation of muscarinic receptors is inhibitory to pituitary-adrenal function.     

Activation by S-adenosylhomocysteine of norepinephrine and serotonin in vitro uptake in synaptosomal preparations from rat brain.

S-Adenosylhomocysteine (10(-7)-10(-5) M) activated norepinephrine (NE) and serotonin (5HT) in vitro uptake in synaptosomal preparations from rat brain, but did not affect dopamine (DA) uptake. When administered to rats (7 mg/kg i.p.), it has the same effect on in vitro NE and 5HT uptake. It did not affect NE and 5HT release.     

Dissolution of the pulmonary collagen of the normal rat by repeated pepsin action]

A non-denaturating method of extracting collagen from Rat lungs was developed. It consists in dissolving the collagen by repeated action of pepsin. Depending on the age of the animal, efficiency values between 50 and 90% are obtained.     

Induction of dolykaryocytes by vesicular stomatitis virus in XC rat cells]

V.S.V. induced polycaryocytes in rat embryonic fibroblasts, transformed by the Prague strain of Sarcoma Rous (XC cells). This fusion is strictly dependent on the expression of the viral genome and is probably due to the incorporation of viral antigens in the cell membrane. The integrity of cellular RNA synthesis is however not required. The fusion is probably due to a membrane structure characteristic of these transformed cells.     

Primary and secondary cerebral lesions produced by kainic acid injections in the rat]

Systematic (i. p.) or intra-amygdaloid injections of kainic acid elicit typical generalised convulsive seizures with typical electrographic correlates. Depending on the survival time and the amount of neurotoxin administered, secondary pathological damage is invariably found in various brain structures removed from the injection site such as various hippocompal fields, midline thalamic nuclei and neocortical layers III and VI. Various lines of evidence are reported which suggest that the secondary pathological damage is not due to the spread of the neurotoxin but to the epileptic status it induces.     

Activation of particle associated rat liver guanine deaminase by lecithin and interferences of lecithin in protein precipitation

Summary Guanine deaminase solubilized from the light mitochondrial fraction of rat liver was activated by lecithin. The activation was proportional to the concentration of lecithin taken in the system. A ratio of 11 between the two constituents (protein and lecithin) was at least necessary for complete precipitation.Acknowledgment. The authors are grateful to Professor P.S.Krishnan, University of Calicut, Calicut, Kerala, for his interest.     

Selective effects of PHA on rat brush border hydrolases along the crypt-villus axis

The mechanism of the toxicity of lectin from Phaseolus vulgaris seeds has been investigated on rat enterocytes. Cell isolation procedures showed a selectivity in the loss of brush border hydrolases; this indicated that the microvilli blebbing was not the only mechanism of action of lectins on rat enterocytes.     

Selective effects of PHA on rat brush border hydrolases along the crypt-villus axis

Summary The mechanism of the toxicity of lectin fromPhaseolus vulgaris seeds has been investigated on rat enterocytes. Cell isolation procedures showed a selectivity in the loss of brush border hydrolases; this indicated that the microvilli blebbing was not the only mechanism of action of lectins on rat enterocytes.     

Electron microscopic study of secretion of chylomicrons in the rat by enterocytes in lymphatic capillary lumen]

Rats were fed on a 20% fat diet; 30 min. or 2 hrs later intestinal jejunal cells were fixed in situ; samples were taken and processed for subsequent study by electron microscopy. Chylomicron secretion was followed from the enterocyte to the lymphatic capillary lumen. Chylomicrons entered the lamina propria through breaks in the basal membrane at intercellular space level. Their penetration into the lymphatic capillary lumen occurred through the open junctions of the endothelial cells normally kept closed by desmosomal formations.     

Pituitary control of androgen synthesis in the rat embryo]

Removal of the hypophysis by decapitation of the 19--or 20 days--old Rat embryo is followed by a significant decrease in the ability of the embryonic testis to synthesize testosterone and androstenedione from acetate in vitro. It is concluded that pituitary-testis relationships first appear at 19 days of intrauterine life.     

Abortive effect of autologous anti-alpha-fetoprotein antibodies in the rat]

Female Commentry Rats 80--85 days old, were immunized by 5 intramuscular injections of Mouse alphafetoprotein (AFP) and then mated. After fertilization a supplementary injections was administered. The animals were bled at different times and killed immediately after the last bleeding on the 19 or 20th day of gestation. Titers of AFP and of autologous anti-AFP antibodies in the maternal blood were determined as well as the AFP concentration in the pooled amniotic fluids from live embryos of each litter. Compared to non-immunized control series, the total of live and dead embryos per litter in animals immunized with Mouse AFP showed no difference. However, the number of live embryos was on the average 50% lower than that in the control series. The serum titers of AFP and of antibodies to autologous AFP in immunized pregnant Rats bearing dead embryos decreased concomitantly with the number of live embryos. The results reported herein demonstrate that the presence of anti-autologous AFP antibodies in pregnant Rats correlates with the interruption of development in a significant proportions of embryos. This suggests that certain spontaneous abortions in the Rat and perhaps in other mammals can be explained by the rupture of immunological tolerance to autologous AFP.