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Biomedical subjects

G R Bratton

Publications and source records attributed to G R Bratton.

51 records · Page 3Linked to original sources
PubMed1983

Effect of canavanine and 2,3-dimercapto-1-propanol (British antilewisite) on the proliferation of Novikoff hepatoma cells in the presence of concanavalin A.

The effect of canavanine and 2,3-dimercapto-1-propanol (British antilewisite, BAL) on the uptake of (3H)-thymidine by Novikoff hepatoma cells, as a measure of DNA formation, was measured in tissue culture in the absence and presence of the mitogen, concanavalin A (Con A). Canavanine and Con A stimulated cell proliferation at low concentrations, and inhibited at higher concentrations. BAL inhibited even at low concentrations. In the presence of a stimulating concentration of Con A, both canavanine and BAL inhibitory effects were amplified. In the presence of a high concentration of Con A and low concentration of BAL the combined effect was substantially greater than the sum of the individual effects. We describe the culture and harvest of Novikoff hepatoma cells, and changes in their morphology when acted upon by the toxic agents used.

Animals↗
PubMedDate not supplied

Lead transport in IEC-6 intestinal epithelial cells.

This study evaluated the use of IEC-6 cells as a model for studying lead (Pb) transport by intestinal epithelial cells (IECs) and examined potential transport mechanisms for Pb uptake and extrusion. Pb accumulation in IEC-6 cells exposed to 5 and 10 microM Pb for up to 60 min was time- and dose-dependent. Reduction of incubation temperature significantly reduced the total cellular Pb content of IEC-6 cells. Simultaneous exposed of cells to zinc (Zn) and Pb resulted in decreased total cellular Pb contents compared to total cellular Pb contents of cells exposed to Pb only. IEC-6 cells treated with ouabain (1 mM) or sodium azide (1 mM) and 5 microM Pb accumulated more Pb than cells exposed to Pb only. Cells treated with p-chloromercuribenzensulfonic acid (50 microM), p-chloromercuribenzoic acid (50 microM), or iodoacetimide (50 microM) accumulated less Pb than cells treated with Pb only. We conclude that Pb uptake by IEC-6 cells depends on the extracellular Pb concentration. Our data suggest that the mechanism of Pb uptake by IECs is complex, and that Pb transport in IEC-6 cells is time- and temperature-dependent, involves sulfhydryl groups, and is decreased by the presence of Zn. Extrusion of Pb is at least partially dependent on metabolic energy.

Animals↗
PubMedDate not supplied

Cadmium exposure results in decreased responsiveness to ethanol.

Adult male Sprague-Dawley rats were maintained on an ad lib diet containing 100 ppm cadmium (Group Cadmium-Diet) or a control diet with no added cadmium. On Day 61, all animals (N = 10/group) were challenged with a single hypnotic dose of ethanol (3.5 g/kg IP), prepared from a 20% v/v solution of tap water and a stock solution of 95% ethanol. The latency from the time of the injection until the loss of the righting reflex was recorded, as well as the latency for recovery of the reflex. The results showed a nonsignificant trend for animals exposed to cadmium to lose the righting reflex less rapidly than controls, and Cadmium-Diet animals regained the righting reflex significantly more rapidly than controls. These findings suggest that the pharmacologic effectiveness of ethanol is altered by chronic exposure to dietary cadmium. The implications of these data for other studies of cadmium/ethanol interactions are discussed.

Animals↗
PubMedDate not supplied

The effects of naltrexone on cadmium-induced increases in oral ethanol self-administration.

Adult male rats were exposed to a standard laboratory diet (N = 20), or an adulterated diet containing 100 ppm added cadmium (N = 20), for 60 days. On Day 61, half the animals from each dietary condition received subcutaneous implants of two 30 mg naltrexone pellets, and the remaining half the animals received identical implants of 30 mg placebo pellets. One week later, animals from groups created by this interaction (Groups Control-Placebo, Control-Naltrexone, Cadmium-Placebo, Cadmium-Naltrexone) were tested in an ethanol self-administration paradigm that presented a 10% ethanol solution (v/v) in both a choice and nonchoice format. The results indicated that cadmium exposure increased the oral self-administration of ethanol in the choice setting where water was offered as an alternative, and the opiate antagonist naltrexone failed to attenuate this effect.

Alcohol Drinking↗
PubMedDate not supplied

Lead attenuates the antipunishment effects of ethanol.

Adult male rats were exposed to a diet containing no added chemicals, or a diet containing 500 ppm added lead (as lead acetate), for 70 days. On Day 71 (training day), after 24 h of water deprivation, all animals were placed in a test apparatus and permitted to make 220 licks for a 5.5 percent (v/v) sucrose in water solution. On Day 72 (test day), all animals received conditioned punishment training where electric shock was delivered to the tongue following every 20 licks of the sucrose and water solution. Prior to commencing punishment training on Day 72, half the animals for the control diet condition (Group Control-Diet-Saline), and half the animals for the lead diet condition (Group Lead-Diet-Saline), received IP injections of saline. Conversely, the remaining half of the animals (Groups Control-Diet-Ethanol and Lead-Diet-Ethanol) received IP injections of 1.5 g/kg ethanol. The results of the conditioned punishment test revealed that animals exposed to a control diet and administered ethanol (Group Control-Diet-Ethanol) engaged in more punished licking and received more shocks than their lead-treated counterparts (Group Lead-Diet-Ethanol). Both of the groups exhibited more punished licking and received more shocks than either of the groups that received saline injections. The possibility that lead contamination may reduce the pharmacologic impact of ethanol is noted.

Animals↗
PubMedDate not supplied

Lead/ethanol interactions. I: rate-depressant effects.

Adult male rats were exposed to a diet containing 500 ppm added lead as lead acetate (group lead-diet) or a control diet containing no added chemicals (group control-diet) for 61 days prior to commencing fixed-ratio 32 (FR 32) lever press training for water reinforcement. After steady state responding was achieved, all animals received serial administrations of acute doses of ethanol prior to the daily training session. Specifically, lead-diet and control-diet rats received i.p. injections of .25, .5, .75, 1.0, and 1.25 g/kg ethanol, in ascending order, alternating daily with injections of saline. The results revealed a dose-dependent rate-depressant effect, with higher doses of ethanol producing more behavioral suppression than lower doses for both groups. In addition, at the dose of 1.0 g/kg it was observed that the suppressive effects of ethanol on schedule-controlled responding were reduced among lead-treated animals relative to controls. These data are discussed in terms of lead-induced attenuation of the pharmacologic effects of ethanol.

Animals↗
PubMedDate not supplied

Ethanol self-administration in rats following exposure to dietary cadmium.

Rats were maintained on an ad lib diet containing 100 ppm cadmium (Group Cadmium-Diet) or a control diet with no added cadmium (Group Control-Diet). After 55 days of exposure to their respective diets, animals were tested for fluid intake using a nonchoice procedure that presented a 15% ethanol solution in the home cage for 5 days. Subsequently, all animals were offered a 10% ethanol solution or tap water in a 3-bottle, 2-fluid choice test in the home cage. This fluid intake test was conducted for a 5 day baseline period, and then again concurrently with avoidance acquisition (14 days) and extinction (4 days) training on a free operant (Sidman) avoidance task that required animals to lever press to avoid electric footshock. After training was terminated the choice test was continued further in the home cage for a 15 day post-avoidance period. Ethanol intake was greater for animals exposed to cadmium on all tests of fluid consumption, and all animals consumed more ethanol during the periods following termination of the stressor (avoidance extinction, post-avoidance) than during the actual period of stress (avoidance acquisition). Interpretive comments focus on the effects of cadmium on stress reactivity, sensory processing, and metabolism.

Alcohol Drinking↗
PubMedDate not supplied

The effects of cadmium on the self-administration of ethanol and an isocaloric/isohedonic equivalent.

During a period of baseline fluid intake recording, adult male rats were presented with a three-bottle, two-fluid choice test that offered either a 10% ethanol solution (v/v) and tap water as alternatives, or a sucrose/quinine solution and tap water as alternatives. The sucrose/quinine solution was equivalent to the ethanol solution both in terms of calories and palatability. After intakes stabilized, half of the animals from each test condition were placed on a diet containing 100 ppm cadmium and the remaining half of the animals were placed on a standard laboratory diet. After 60 days of exposure to their respective diets, all animals were presented their earlier test solutions, both in a nonchoice and choice format. The results from the choice test indicated that although cadmium treatment did not produce a clear preference for ethanol over water, cadmium exposure was associated with a significant increase in ethanol consumption. Moreover, the self-administration of the isocaloric/isohedonic equivalent (sucrose/quinine solution) was unaffected by cadmium contamination. These data are discussed in terms of their implications for both nutritional and sensory-impairment accounts of metal-related changes in the volitional intake of ethanol.

Alcohol Drinking↗
PubMedDate not supplied

Behavioral antagonism between lead and cadmium.

Adult male rats were exposed to one of four dietary conditions for a period of 60 days. Group Control-Diet received a diet containing no added lead or cadmium, group Lead-Diet received a diet that contained 500 ppm added lead, group Cadmium-Diet received a diet that contained 100 ppm added cadmium, and group Lead-Cadmium-Diet received a diet that contained both 500 ppm added lead and 100 ppm added cadmium. Subsequent to exposure, animals were tested in a Digiscan activity monitor. Animals were then sacrificed and metal concentrations were determined in blood and brain. The results from this experiment showed that lead alone increased movement and vertical activity. Cadmium alone decreased movement and increased rest time. Cotreatment with lead and cadmium failed to produce behavioral differences relative to controls; thus, it seems that the changes in activity caused by one metal are antagonized by the other. Results from the analyses of residues in tissues revealed that blood lead concentrations were lower in the cotreatment condition than the lead along condition. However, brain residue accumulations were not different for these two exposure conditions. There was no evidence that the presence of lead attenuated increases in cadmium residues in blood or brain. Overall, the residue data agree with a central, as contrasted with a peripheral, account of lead/cadmium interaction effects, at least as relates to behavior. Because lead and cadmium were additive with regard to producing decreased body weights, it seems that the toxic effect of these metals is antagonized by cotreatment in some instances, and augmented in others.

Animals↗