摘要:

A cytogenetic study was conducted on cultured lymphocytes from a group of 60 male volunteers to determine the baseline of chromosomal aberrations in nonchemical workers. Only males were included in the study to avoid any sex effects on the results. Blood samples were collected from each man every 13 w (quarterly) over a period of 12 m. A single batch of culture medium was used for the entire study. The influence of storing the blood samples prior to culture, donor's age, cigarette smoking, and seasonal variation on lymphocyte mitotic index and chromosomal aberration yield was analyzed. A significant decrease in mitotic activity was observed in cultures from samples stored for 3 d at room temperature (22 ± 1°C). Storing of samples at refrigerator temperature (4 ± 1°C) for up to 3 d prior to culture did not affect lymphocyte growth. Although the mitotic index was found to be inversely proportional to the age of the donors, a significant influence of age on total cytogenetic aberrations was not detectable. A group of 15 smokers appeared to have higher number of chromosomal aberrations; however, the difference in mean mitotic activity between lymphocytes of the two groups was not statistically significant. No detectable seasonal influence was found on any chromosomal aberration category except in the number of chromatid gaps. The mitotic indices of the first quarter cultures, on the other hand, showed significant differences from the other three quarters. The chromosomal aberration baseline of the group was not strikingly different from the ones reported by other investigators. Four quarterly samplings of the group indicated that there was about as much cytogenetic variation in different samples from the same subject as there was between subjects sampled at the same time.

ISSN:0098-4108    

DOI:10.1080/15287398609530828

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Transient suppression of splenic natural killer (NK), natural cytotoxic (NC), and peritoneal macrophage cytotoxicity was observed following a single injection of 3‐meth‐ylcholanthrene (3‐MC) into C3H/HeN mice. Natural killer cell activity was depressed by 30–60% 4–6 d after injection of 1.0 mg 3‐MC. Levels of NK reactivity returned to normal 8 d post 3‐MC injection, and no suppression of natural killing was seen when tested 6 wk after 3‐MC treatment. 3‐MC did not affect Propionibacterium acnes augmentation of NK cell activity when tested both 6 d and 6 wk after carcinogen injection.

ISSN:0098-4108    

DOI:10.1080/15287398609530829

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Administration of benzene‐soluble fraction (FAE) and benzene‐insoluble fraction (FAR) of fly ash for 3 consecutive days to rats significantly raised cytochrome P‐450 levels, aryl hydrocarbon hydroxylase (AHH) activity, and glutathione S‐transferase activity in liver. This treatment also significantly increased pulmonary AHH and glutathione S‐transferase activity. Intratracheal administration of FAR (5 mg/100 g body weight) alone for 6 consecutive days also significantly increased hepatic cytochrome P‐450 levels and the activity of glutathione S‐transferase. Intragastric administration of retinyl palmitate (5000 IU/100 g body weight), along with intratracheal FAE and FAR administration, significantly reduced P‐450 levels, activity of glutathione S‐transferase in liver, and activity of AHH and glutathione S‐transferase in lung of rats. Intraperitoneal administration of citrate (40 mg/100 g body weight) along with FAR significantly reduced FAR‐induced increase in hepatic cytochrome P‐450 levels and glutathione S‐transferase activity. The activity of AHH was not affected by these treatments.

ISSN:0098-4108    

DOI:10.1080/15287398609530830

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

To determine the neurotoxic effects of organophosphorus compounds in turkeys, adult birds were given a single oral dose of 125, 250, 500 mg/kg triorthotolyl phosphate (TOTP) or a single subcutaneous dose of 0.4 mg/kg O,O'‐diisopropyl phosphorofluoridate (DFP). At 24 h after dosing with TOTP, neurotoxic esterase activity was found to be inhibited in a dose‐related manner, as were the activities of blood cholinesterase and liver cholinesterase. Clinical signs of neuropathy appeared within 2 wk in TOTP‐treated groups of birds with neurotoxic esterase activities at 59 ± 3% (125 mg/kg), 47 ± 7% (250 mg/kg) and 33 ± 3% (500mg/kg) of control values (mean ± SEM,n= 5) at 24 h after dosing. Signs appeared earlier in turkeys given DFP. Histological examination revealed only mild lesions of delayed neurotoxicity in birds given either TOTP or DFP.

ISSN:0098-4108    

DOI:10.1080/15287398609530831

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

It has been established that the major metabolic pathway for chlordecone (CD)(Ke‐pone) both in humans and in the Mongolian gerbil is bioreduction of this organo‐chlorine pesticide to chlordecone alcohol (CDOH) in the liver. In the present study we developed a gas‐liquid chromatography assay to measure the enzymatic reduction of CD to CDOH in vitro and characterized “CD reductase” activity in gerbil liver cytosol. CD reductase is a cytosolic enzyme readily detectable in liver samples prepared from humans, rabbits, and gerbils, the only species of many tested that convert CD to CDOH in vivo. Gerbil CD reductase exhibited aKmof 2.6 μM, aVmaxof 0.14 nmol/min, and a pH optimum of 6.5. The enzyme activity required NADPH, was sensitive to thiol reagents, and was distributed in all tissues with the highest activities found in the liver, intestine, and kidneys. These results are consistent with CD reductase belonging to the family of enzymes referred to as the “aldo‐keto reductases.” However, unlike previously described reductases, CD reductase was undetectable in rats, mice, hamsters, or guinea pigs and was insensitive to the model aldehyde and ketone reductase inhibitors, phenobarbital and quercetin, respectively. In addition, CD reductase activity in liver was increased by 38% (p< 0.01) following treatment of gerbils with CD. We conclude that CD reductase is a novel aldo‐keto reductase that is uniquely inducible by its substrate.

ISSN:0098-4108    

DOI:10.1080/15287398609530832

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Mirex (dodecachlorooctahydro‐1,3,4‐metheno‐2H‐cyclobuta[cd]pentalene) is a hepatic tumorigen that is shown to cause marked disturbances in hepatic cell ploidy in rodents. Kinetic measurements of [14C]mirex binding were performed in freshly prepared diploid (DP) and polyploid (PP) hepatocytes, as well as in erythrocytes, under controlled conditions. The binding of mirex to hepatocytes, irrespective of their ploidy, was partially Na+‐dependent and totally Ca2+‐independent. Variations in temperature and pH appeared to significantly inhibit mirex binding; the optimum binding was seen at 37° C under physiological pH. The saturation kinetic data revealed that PP cells were saturated at a very low concentration of mirex (two‐ to threefold) compared to DP, exhibiting a high‐affinity binding of mirex to PP with a lowKm(347 nM) andVmax(102 nmol/mg · min). TheKm(550 nM) andVmax(340 nmol/ mg · min) values determined for DP cells were of higher magnitude, like those of erythrocytes (Km, 879 nM;Vmax, 330 nmol/mg · min), indicating that distinct differences exist in the binding affinities of three cell types. However, erythrocytes and DP cells showed close similarity in theirVmaxvalues. Interestingly, mirex levels in the lipid compartments of DP and PP cells revealed no apparent differences. The results are discussed in terms of the possible susceptibility of PP cells and their role in the initiation of toxic response leading to hepatotumorigenesis in rodents.

ISSN:0098-4108    

DOI:10.1080/15287398609530833

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Rats were treated with chlordecone, mirex, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), and respective solvent vehicle. Under urethane or pentobarbital anesthesia, the bile duct was cannulated and radioactive morphine, imipramine, or ouabain was given by segmented retrograde intrabiliary injection. The spectrum of inhibition of biliary excretion by chlordecone and mirex were similar in that morphine glucuronide and in part polar imipramine metabolite recoveries in bile were decreased; ouabain recovery was unaffected. TCDD was different in that it markedly decreased the recovery of ouabain. Thus, it appears that chlordecone, mirex, and TCDD inhibit the canalicular transport of the glucuronide metabolites of morphine and imipramine into bile, and TCDD affects in addition the canalicular transport of ouabain into bile.

ISSN:0098-4108    

DOI:10.1080/15287398609530834

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The separate and combined effects of protein deprivation and benomyl [(methyl 1‐butylcarbomoyl)‐2‐benzimidazole carbamate] exposure were studied in the pregnant rat fed a diet containing 24% (control) or 8% (deficient) casein throughout gestation. Within each diet group, subgroups were gavaged at 31.2 mg/kg body weight with benomyl or corn‐oil carrier only on d 7–16 or 7–21 of gestation. No effects on the skeleton were seen. Benomyl exposure in the last 2 wk in dams fed the 24% casein diet resulted in a high incidence of fetal brain anomalies. This effect did not occur in those with benomyl exposure during the period of organogenesis only and was reduced in groups fed the protein‐deficient diet. Exposure to benomyl in the last 2 wk in the protein‐deprived rat resulted in a decrease in the weight of the fetal heart in excess of that attributable to diet alone. Lungs were a smaller portion of body weight in fetuses of benomyl‐treated dams in both diet groups. The teratogenic effect on the brain in animals exposed to benomyl in wk 2 and 3 of gestation suggests that screening for teratogenic effects during organogenesis only may be insufficient.

ISSN:0098-4108    

DOI:10.1080/15287398609530835

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

One month after termination of a 3‐mo exposure of rats to cadmium (Cd in drinking water at a concentration of 50 mg/l), the effects of dithiocarbamate analogs on the excretion and distribution of the cadmium were determined. Sodium salts of three dithiocarbamates [sodium bis(hydroxyethyl) dithiocarbamate, DEDTC; sodium N‐methyl‐D‐glucamine dithiocarbamate, MGDTC; and sodium 4‐carboxamidopiperidine dithiocarbamate, INADTC] were given to rats ip 2 times at 2.46 mmol/kg. In the 12 h following administration of the first injection of DEDTC, cadmium excretion via the urine amounted to 15.8 μg and via bile amounted to 124.4 μg Cd. Following administration of MGDTC, the urinary and biliary excretions of cadmium were 14.5 and 47 μg, respectively, while in the case of INADTC the corresponding values were 23.6 and 7.9 μg cadmium. In control animals the urinary and biliary excretion per 12 h reached 0.09 and 0.12 μg Cd. Gel permeation chromatography (GPC) analysis of bile revealed differences in the distribution of Cd in the elution fractions after the first injections of the individual dithiocarbamates. For all three dithiocarbamates, significant decreases of the concentrations of cadmium in the liver and kidney were found. DEDTC (but neither of the other compounds) increased the concentration of cadmium in the brain from control levels of 49 ± 5 ppb to 105 ± 16 ppb.

ISSN:0098-4108    

DOI:10.1080/15287398609530836

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The dithiocarbamate enhancement of the biliary excretion of cadmium in rats loaded with cadmium (by either the oral or sc route) was found to be strongly dependent on the structure of the groups attached to the nitrogen atom of the dithiocarbamate moiety. Those dithiocarbamates containing hydroxyl‐bearing attached groups were found to be capable of causing the greatest enhancement of the cadmium content of the bile. For the compounds of this type that were examined, this enhancement of biliary cadmium content varied from 30‐fold to over 2000‐fold. No enhancement of the biliary excretion of cadmium was found subsequent to the administration of sodium diethyldithiocarbamate, though this compound is known to cause a significant increase in the fecal excretion of cadmium.

ISSN:0098-4108    

DOI:10.1080/15287398609530837

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor