Mutagenicity and cytotoxicity of 2-chlorobenzylidene malonitrile (CS) and metabolites in V79 Chinese hamster cells

The genotoxicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS) to V79 Chinese hamster cells was investigated using the induction of gene mutations, micronuclei and DNA repair synthesis as biological endpoints. CS efficiently induced micronuclei and mutants resistant to 6-thioguanine in these cells, but it did not elicit DNA repair synthesis. Induction of micronuclei and mutants showed very similar courses of concentration dependence, suggesting that both events were caused by the same mechanism. The hydrolysis products of CS, o-chlorobenzaldehyde and malononitrile dit not induce micronuclei and were much less cytotoxic than CS. The observation of heritable genetic changes in cells exposed to CS in the absence of detectable DNA damage suggests that the genetic effects of CS are not caused by an interaction of the compound or its hydrolysis products with DNA. It appears more likely that the mutagenic activity is the consequence of effects of CS on the mitotic apparatus of the cells causing chromosomal aneuploidy.     

Effects of CS Duration and Instructional Set on Cardiac Anticipatory Responses to Stress in Field Dependent and Independent Subjects

The study showed that within a modified delayed conditioning paradigm the shape of the anticipatory cardiac response to shock can be modified by changing the CS duration. When the tone (CS) duration was only 4 sec, there was a significant HR acceleration. With the CS duration increasing stepwise, from 4 to 12 sec, the anticipatory cardiac response to the UCS became biphasic. The acceleratory component of this response was bound to the CS and time locked, and, on the average, reached its peak within 5 sec after the onset of the CS. The deceleratory component was directly related to the length of the time interval between the onset of the CS and the UCS: there was no anticipatory deceleration when the tone duration was 4, 5, or 6 sec; the most pronounced deceleration was observed during the 10 sec interval. Instructional sets did not significantly affect cardiac activity by themselves, but did influence responses in interaction with the individual difference variable of field dependence; this was found to be the case only on the first trial. Field dependence was also a meaningful variable, and accounted for some of the differences in the patterns of HR responding in anticipation of shock.     

Comparison of cytotoxicity of mercury-selenium and mercury compounds on cultured cells

In vitro effects of mercury-selenium (Hg-Se) compounds, as compared with their original mercury compounds, against growth and viability of HeLa cells were studied. A water-soluble, ethanol-insoluble black complex (GX) formed from HgCl2, Na2SeO3 and GSH was less toxic than HgCl2, but the cytotoxicity of bis(methylmercuric) selenide (BMS) seemed to be similar to that of methylmercury. This may be due to the instability of BMS; i.e., there is a possibility that BMS decomposed to methylmercury and selenium under our culture conditions.     

Enhancement of memory by a cholinesterase inhibitor associated with muscarinic receptor down-regulation

Rats trained on a passive avoidance task 24 hours following a single intraperitoneal injection of diisopropyl fluorophosphate (DFP, 1.2 mg/kg) showed enhanced retention when tested 7 days later. In a parallel group of rats, reduced cortical [3H] quinuclidinyl benzilate binding was demonstrable 24 hours following DFP administration. The association of reduced muscarinic receptor binding and enhanced performance on a memory task contradicts previous reports which suggested that retention was impaired by treatments which down-regulate muscarinic receptors. This contradiction may be reconciled if pre-synaptic factors such as agonist availability are considered in conjunction with post-synaptic receptor effects.     

Effect of alcohol intake on some disturbances induced by chronic exposure to carbon disulphide in rats. I. Behavioural alterations

Female white Wistar rats were exposed to CS2 vapour (0.8 mg CS2/1 air) 11 months and to 10% ethanol as the only drinking liquid for the last 3 months of exposure. Spontaneous exploratory motor activity (SEMA), open-field behaviour, passive avoidance performance and the avoidance acquisition were tested. Ethanol did not change the exploratory motor activity and behaviour of CS2-exposed rats in the open-field and passive avoidance tests but it affected their performance in the conditioned avoidance test. The analysis of data suggests that ethanol may adversely affect memory and learning ability in CS2-exposed rats.     

Development of the motor system: Hopping rats produced by prental irradiation

Irradiation of prenatal and infant rats resulted in a spectrum of highly reproducible nervous system malformations associated with locomotor abnormalities difficult to correlate with morphologic findings. Fetal rats exposed to 150 R on the 13th, 14th, or 15th day of gestation were born with a hopping gait, paired hind and forelimbs moving in unison instead of the normal alternating mode. Some animals switched partly or completely to an alternating gait of forelimbs, rarely hind limbs. Rats irradiated on the 12th, 16th, or 17th day did not hop. The problem: Was the hopping related to the brain or spinal cord? Hopping rats could jump to a level or tilted landing platform. Their forelimbs tactually placed independently of each other, whether they hopped or not, but the hind limbs scratched synchronously. Thoracic cord transection led to crossed extension hind-limb reflexes in normal rats, and simultaneous withdrawal of hind limbs in hopping rats, in response to bilateral pinprick. The dorsal horns, especially Rexed's laminae I–VI, and sometimes the most dorsal part of VII, which were being formed in the 13- to 15-day period as shown by tritiated thymidine autoradiography, were underdeveloped. This was due to failure to make restitution of residual dorsal proliferative cells remaining after radiation. Some neurons destined for the dorsomedial parts of the ventral horns may have been lost after the 13th- and 14th-day irradiation, but not the 15th. Precisely how dorsal horn deficiencies could affect the spinal locomotor generator, presumed to be more ventrally situated, it is not yet known. Nor has the exact nature of the suprasegmental adaptation to the hopping mechanism and switching to normal forelimb gait been worked out.     

Purkinje cell activity during classical eyeblink conditioning in decerebrate guinea pigs

Purkinje cells are the sole output from the cerebellar cortex and play a critical role during classical eyeblink conditioning. The present study revealed for the first time a learning-related change in individual Purkinje cell activity during successive eyeblink conditioning in decerebrate guinea pigs which permitted continuous single unit recording from the simplex lobe of the cerebellar cortex. The pair-conditioned group received paired presentation of the conditioned stimulus (CS) and unconditioned stimulus (US) until the frequency of the conditioned response (CR) exceeded 80%. The control group received a comparable number of the CS and US in a pseudorandom fashion. Responses of Purkinje cells to the CS were classified into four types: excitatory, inhibitory, a combination of the two, or no response. Approximately half of the recorded cells from both groups changed their response type at various conditioning stages. The firing frequency of a Purkinje cell to the CS showed a tendency to decrease in the pair-conditioned group, while it had a tendency to increase in the pseudoconditioned group. This learning-related difference in change of response type was attributable to a difference in the change between the no response and the inhibitory response types. Correlation analysis of the temporal pattern between the neural activity and the CR revealed that most of the cells that developed an inhibitory response by paired conditioning acquired the CR-related temporal pattern. These results suggest that the learning-related Purkinje cells gain an inhibitory response with a temporal pattern correlated with the CR topography.