Very low sister-chromatid exchange rate in Seventh-Day Adventists

42 Seventh-Day Adventists (SDAs) and 42 controls matched for sex, age and occupation had their sister-chromatid exchange (SCE) examined in peripheral blood lymphocytes. This was done to examine if the SCE frequency was lower in this group of people, who are known to have a decreased cancer risk compared to the general population. The average SCE/cell in 30 cells from each person was 5.54 +/- 0.07 (mean +/- standard error of the mean) for the SDAs and 8.00 +/- 0.15 for the controls, the difference being statistically significant (p less than 0.00001). No difference in SCE frequency was found between SDAs eating only an ovo-lacto-vegetarian diet and those eating some fish or meat. The mitotic index (MI) was significantly higher and the replication index (RI) was significantly lower in SDAs than in controls. No correlation was found between gamma (a statistical transformation of SCEs/cell) and MI or RI within the groups of SDAs or controls. In the pooled data there was a negative correlation of gamma and MI and a positive correlation of gamma and RI. Of the interpersonal variation in gamma 8% and 14% could be explained by MI and RI. The finding of a lower SCE frequency in a group of SDAs who have a low risk of cancer might indirectly indicate a relation between SCE and cancer and encourages further studies of SCE and diet.     

Effects of hydroxyurea on the mitotic activity and the G2 phase in hairless mouse epidermis

Hairless mice were given 5 mg hydroxyurea (HU) intraperitoneally (i.p.) followed by 0.15 mg Colcemid at various times after HU. The animals were killed at 2 and 4 hr after Colcemid, the epidermal mitotic counts in dorsal skin were determined and the mitotic rates calculated. These were compared with the normal mitotic rates, and the ratios between the results from HU-treated and -untreated animals were calculated. Hydroxyurea caused a considerable reduction in the mitotic rate with a trough at 6 hr, followed by a wave of increased mitotic rate with a peak at 14 hr, followed by a secondary drop at 20 hr, and then a return to normal. Another group of mice were given HU only, and the fraction of epidermal cells in G2 was measured by flow cytometry. From these animals, without previous injection of Colcemid, we also determined the mitotic counts and calculated the mitotic durations. Cells piled up in G2 for the first 6 hr after HU injection, then the G2 compartment was emptied. The results are discussed in relation to previous results from this department showing the effect of the same dose of HU on DNA synthesis in the same mouse strain. It is concluded that HU not only blocks or retards DNA synthesis in epidermal cells, but also affects the movement of cells through G2 and M. The cell kinetic effects of HU thus seem to be very complex.     

Seasonal Rates of Methane Oxidation in Anoxic Marine Sediments

Methane concentrations and rates of methane oxidation were measured in intact sediment cores from an inshore marine sediment at Jutland, Denmark. The rates of methane oxidation, determined by the appearance of ¹⁴CO₂ from injected ¹⁴CH₄, varied with sediment depth and season. Most methane oxidation was anoxic, but oxygen may have contributed to methane oxidation at the sediment surface. Cumulative rates (0- to 12-cm depth) for methane oxidation at Kysing Fjord were 3.34, 3.48, 8.60, and 17.04 μmol m⁻² day⁻¹ for April (4°C), May (13°C), July (17°C), and August (21°C), respectively. If all of the methane was oxidized by sulfate, it would account for only 0.01 to 0.06% of the sulfate reduction. The data indicate that methane was produced, in addition to being oxidized, in the 0- to 18-cm sediment stratum.     

EFFECTS OF 5,6-DIHYDROXYTRYPTAMINE ON MONOAMINERGIC NEURONES IN THE CENTRAL NERVOUS SYSTEM OF THE RAT

—The injection of 50 μg of 5,6-dihydroxytryptamine (5,6-HT) into a lateral ventricle of the rat depleted the spinal cord and various regions of the brain of indoleamines (presumably 5-HT) and 5-hydroxyindole acetic acid. The concentrations of 5-HT were measured by two different methods: the formation of a fluorescent derivative with o-phthalaldehyde, and the native fluorescence in hydrochloric acid. When the results of both methods were compared on the pons and medulla 4 days after injecting 5,6-HT, the loss in indoleamine appeared to be greater when o-phthalaldehyde was used. This suggests that the two methods may be measuring different compounds. According to both methods, the loss of 5-HT persisted for several days after the injection of 5,6-HT, but by 2 months 5-HT concentrations (measured only by the native fluorescence procedure), had recovered to near-normal values. The depletion of 5-HT was most pronounced in regions adjacent to the ventricular system and in the spinal cord. Initially, caudate and septum were more affected on the side of the injection, and later showed some permanent atrophy. The injection of up to 50 μg of 5,6-HT did not lead to any significant loss of noradrenaline or dopamine from the brain, or to any reduction in the activity of the enzyme tyrosine hydroxylase. The drug was a potent inhibitor of the uptake of [³H]5-HT by brain slices, but was less effective in inhibiting catecholamine uptake systems. These observations suggest a preferential action on tryptaminergic neurones. Larger doses of 5,6-HT caused a loss of catecholamines and tyrosine hydroxylase from the brain, and were severely toxic.     

EFFECTS OF AMINO-OXYACETIC ACID ON [3H]GABA UPTAKE BY RAT BRAIN SLICES

Abstract— The effect of amino-oxyacetic acid on the uptake of [³H]GABA by rat brain slices was studied. When added simultaneously with [³H]GABA, amino-oxyacetic acid had no significant effect on [³H]GABA uptake. However, preincubation of brain slices with amino-oxyacetic acid prior to addition of [³H]GABA produced inhibition of uptake, which increased with longer duration of preincubation. The inhibitory effect of amino-oxyacetic acid was maximal at 2 mM concentration and concentrations sufficient to inhibit significantly GABA:glutamate transaminase (10^--⁶ M) had no effect on [³H]GABA uptake. D-Cycloserine and β-hydrazino-propionic acid also inhibited [³H]GABA uptake, but the amounts required were considerably in excess of those needed to inhibit GABA:glutamate transaminase. 4-Deoxypyridoxine inhibited [³H]GABA uptake, whether given in vivo or in vitro , and the inhibitory effect of amino-oxyacetic acid was reversed with pyridoxine. GABA transport appears to be dependent on pyridoxal phosphate and interference with this function of the vitamin is suggested as the basis for the inhibitory effect of amino-oxyacetic acid on [³H]GABA uptake.     

Induction of cognitive impairment by scopolamine and noncholinergic agents in rhesus monkeys.

In primates, treatment with scopolamine impairs performance of a spatial delayed response task in a way which mimics deficits seen spontaneously in aged primates and demented patients. Despite their efficacy in reversing scopolamine induced disruption, the effects of cholinergic agonists on cognition in aged primates and dements are unimpressive, suggesting that other neurotransmitter systems are also involved in this type of deficit. We have induced a scopolamine-like impairment of spatial delayed response performance in rhesus monkeys using phencyclidine (0.1-0.2 mg/kg i.m.), lorazepam (0.4-0.6 mg/kg s.c.) or tetrahydrocannabinol (1-4 mg/kg p.o.), but not amphetamine (0.1-0.4 mg/kg i.m.), yohimbine (0.1-1.0 mg/kg i.m.) or morphine (2-4 mg/kg i.m.). Our findings suggest that disruption of specific neurotransmitter systems other than acetylcholine may contribute importantly to cognitive decline in aging and dementia.