摘要:

In order to evaluate the influence of age on 2‐acetylaminofluorene (2‐AAF) carcinogenesis, female BALB/c mice were fed diets containing 500 ppm 2‐AAF for 6 mo, starting at 1, 7, or 13 mo of age. Croups of mice were killed immediately, 3 or 6 mo after termination of treatment, or were allowed to complete their life span. Mice corresponding to the age of each sacrifice group of the 2‐AAF‐treated mice and a life‐span group were also included as controls. The study was moved to a different animal room area after 25 wk into the study. Thus, certain treatment groups were replicated to evaluate the impact of the change in environment. Controls and the young 2‐AAF‐treatment group killed at 7 mo of age were replicated twice in the new animal room at 6‐mo intervals. Similarly, controls and the mid‐aged treatment group killed at 13 mo of age were repeated once in the new animal room. This resulted in mice of each age/treatment group being treated simultaneously in the same room and killed as soon as treatment was stopped. The main histopathologic responses to 2‐AAF were observed in the urinary bladder, liver, and mammary glands. In all three replicates urinary bladder hyperplasia was less severe when young mice were treated than when mid‐aged or old mice were treated. In contrast, there was no clear influence of age on bladder tumorigenesis, although replicate variation in this response was very great.

ISSN:0098-4108    

DOI:10.1080/15287398709531056

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Absorption of cadmium and lead from the gastrointestinal (GI) tract of adult rats was measured after gavage with solutions of109Cd or210Pb. Before the radionuclide gavage, animals were either fed or fasted for 24 h, or fasted and given a supplemental gavage of ferric or ferrous iron. Fasting caused a slight increase in109Cd absorption that was not statistically significant; ferrous iron caused a three‐fold increase; and ferric iron increased absorption 14‐fold. In contrast, fasting increased210Pb absorption fivefold, and the oxidizing agents ferric iron and quinhydrone blocked the effect of fasting. Gavage of 8‐d‐old rats with109Cd and either ferric or ferrous iron doubled the amount of cadmium retained in the carcass and substantially decreased the amount retained in the GI tract. Some of the large fraction (60–70%) of109Cd stored in the mucosa of the intestine was absorbed into the body with time. An excess of ferric iron had an opposite effect on the retention of lead in the carcasses of 8‐d‐old rats, decreasing it from 53% of the gavaged dose to 3%; the effect on the amount retained in the intestine was similar, decreasing it from 76% to 8%. These results suggest that the mechanisms for transport of cadmium and iron across the intestine may be similar in the adult and neonatal rat, but that the oxidizing effect of ferric iron on cadmium absorption is much greater in the adult.

ISSN:0098-4108    

DOI:10.1080/15287398709531057

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Sublethal doses of CdCl2(3 mg/kg iv), HgCl2(2 mg/kg iv), or NaVO3(6 mg/kg iv) did not alter the content of reduced glutathione (GSH) in the livers of mice during the 24‐h observation period. In the kidneys, a tendency to increased GSH content was seen, especially after HgCl2treatment; in lung and brain the GSH levels were significantly lowered upon the treatment with all three metals. The activities of GSH S‐transferase toward an aryl substrate (CDNB; 1‐chloro‐2,4‐dinitrobenzene) was enhanced in all tissues by the administration of HgCl2> NaVO3> CdCl2. The activity of GSH S‐transferase toward an epoxide substrate [1,2‐epoxy‐3‐(p‐nitrophenoxy)pro‐pane was only measurable in the livers and was inhibited 1 and 2 h after the administration of HgCl2and NaVO3. It is concluded that sublethal doses of CdCl2, HgCl2, or NaVO3do not impair the GSH concentration and GSH‐conjugating enzyme activities toward the aryl substrate in different target organs of their toxicity, which is in contrast to results obtained in vitro.

ISSN:0098-4108    

DOI:10.1080/15287398709531058

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The effects of trimethyltin (TMT) on the mouse adrenal histology and its relationship with neuropathology occurrence was studied. Young, male CD‐I mice were divided into three groups: group I, injected on 3 consecutive days with 1.0 mg TMTIkg body weight (b.w.); group II, injected on 2 consecutive days with 7.5 mg TMT/kg b.w.; and group III, injected with a single acute dose of 3.0 mg TMT/kg b.w. Control animals were injected with saline solution. The brain and adrenal glands were sampled for light‐microscopic examination. Although all animals received the same total amount of TMT, pathological changes in the granule cells of the fascia dentate appeared to be group III > group II > group I, suggesting that acute exposures produced a more severe damage to the fascia dentate neurons. Likewise, the adrenal weights of the animals were group III > group II > group I 3 = control. Significant proliferation and enlargement of the eosinophilic or the “X zone” were observed in the TMT‐treated, particularly groups II and III, animals. The expansion of the eosinophilic cell layer (X zone) was accomplished at the expense of the cortical fasciculata cells. Transformation of fasciculata cells into eosinophilic cells could also be demonstrated. As the eosinophilic cells are known to be active in corticosterone production as seen in stress situations, the proliferation of these cells may reflect a feedback response to the hippocampal hyperexcitation.

ISSN:0098-4108    

DOI:10.1080/15287398709531059

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The ability of a number of metals and organic chemicals to induce metallothionein (MT) synthesis in primary cultures of rat hepatocytes was tested to determine whether MT induction in vivo results from a direct effect of the agent on the liver or as a result of an indirect, physiologic response to the agent. Hepatocytes were exposed to metals [zinc (Zn), cadmium (Cd), mercury (Hg), manganese (Mn), lead (Pb), cobalt (Co), nickel (Ni), and vanadium (V)] or organic compounds [ethanol, urethane, L‐2‐oxothiozolidine 4‐carboxylate (L‐OTCA), or dexamethasone] and were assayed for metallothionein by the Cd/hemoglobin radioassay. Cell viability was monitored by protein synthesis activity and cellular K+concentration. Increases in MT concentrations were noted for Zn (22‐fold), Hg (6.4‐fold), Cd (4.8‐fold), Co (2.4‐fold), Ni (2.2‐fold), and dexamethasone (4.5‐fold). However, even at maximum tolerated concentrations, Mn, Pb, V, ethanol, urethane, and L‐OTCA did not increase MT. The results indicate that Zn, Cd, Hg, Co, Ni and dexamethasone induce MT in vitro and thus are direct inducers of MT synthesis in hepatic tissue. In contrast, Mn, Pb, ethanol, urethane and L‐OTCA, which did not increase the MT content of hepatocytes, apparently do so in vivo by an indirect mechanism.

ISSN:0098-4108    

DOI:10.1080/15287398709531060

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Fischer 344 rats (810 of each sex) were divided into treatment groups and fed diets containing 0, 10, 40, 600, 1200, or 2400 ppm sulfamethazine. Serum samples were analyzed for levels of thyroid‐stimulating hormone (TSH), total thyroxine (T4), total triiodothyronine (T3), and T3 uptake after 12, 18, or 24 mo of continuous dosing. There were no statistically significant differences in T3 levels or percent T3 uptake for either sex after any of the exposure periods. The serum T4 levels were lower (p< 0.05) for females dosed at 1200 and 2400 ppm for 18 mo and for males dosed at 600, 1200, or 2400 ppm sulfamethazine for 24 mo than for those dosed at levels of 40 ppm or less. Serum TSH levels showed a general increasing trend (but not statistically significant) among animals receiving 600 ppm or more sulfamethazine. There was a significant dose‐related reduction in (T3 + T4)/TSH ratio for both sexes (p< 0.05) after 18 and 24 mo of exposure at dose levels of 600 ppm or more. A lack of response at 12 mo may have been due to the shorter treatment time. At each sacrifice period both sexes of rats fed sulfamethazine at 1200 and 2400 ppm had significantly heavier (p< 0.05) thyroid weights than animals fed control diet. The heavier thyroid weights in the dosed animals may have resulted from increased TSH levels. The cause of reduction in serum T4 was not clearly evident. Therefore, the thyroid hormone to pituitary feedback mechanism apparently compensated for sulfamethazine effects in most animals. This would suggest that the thyroid gland was not irreversibly affected.

ISSN:0098-4108    

DOI:10.1080/15287398709531061

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

The effect of subchronic administration of morpholine oleic acid salt (MOAS) was studied in B6C3F1mice. The dose levels of MOAS used were 0%, 0.15%, 0.3%, 0.6%, 1.25%, and 2.5% in drinking water. Reduced weight gains were noted in both sexes in the 2.5% group as compared to controls, but reductions were not significant. Water consumption values showed a dose‐related tendency for a decrease in both females and males. Urine analysis showed significant elevation of specific gravity in the males in the 0.6%, 1.25%, and 2.5% groups and the females in the 1.25% and 2.5% groups. Significant elevation of plasma urea nitrogen was observed in males of the 1.25% and 2.5% groups and in females of the 0.6%, 1.25%, and 2.5% groups. The relative weight of the kidneys showed a dose‐dependent increase that was statistically significant for the 1.25% and 2.5% MOAS groups in both sexes. Except for cloudy swelling of the proximal tubules of the kidneys in mice on the 2.5% regimen, no treatment‐related histopathological alterations were observed in organs of either sex.

ISSN:0098-4108    

DOI:10.1080/15287398709531062

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Male Sprague‐Dawley rats were given a single, usually lethal, dose of 2,3,7,8‐tetra‐chlorodibenzo‐p‐dioxin (TCDD, 125 μg/kg ip in corn oil), or vehicle alone. Twenty‐four hours after ip administration of TCDD the animals received an ip injection of14C‐labeled glucose, and the time course and amount of exhalation of14CO2were monitored for 8 h continuously and once daily for 20 min for the subsequent 5 d. TCDD treatment reduced the amount of14CO2exhaled within 8 h after the injection of [14C]glucose by 33%, as compared to pair‐fed controls. Blood levels of radioactivity were affected by TCDD accordingly. No particular organ appeared to act as a sink for the radioactivity not exhaled during these 8 h by the treated animals. TCDD (125 μg/kg) induced significant changes in the disposition of radioactivity in heart and brown adipose tissue between 25 and 125 min after the iv injection of [14C]glucose. The areas under the curve of [14C]glucose‐derived radioactivity were the same after either iv or ip injection in the blood of TCDD‐treated rats, allowing a direct comparison of experiments with iv or ip injection of [14C]glucose. The half‐lives of radioactivity in the exhaled air and in feces of treated animals were greatly elevated during the 5 d following administration of [14C]glucose. These results indicate that TCDD induces in rats, within 24 h after dosing, alterations in the metabolism of glucose that preceded changes in insulin homeostasis, because hypoglycemia and hypoinsulinemia in rats do not occur until about a week after TCDD treatment. Since overt signs of acute toxicity (reduced feed intake and body weight loss) are also not noticeable until several days after a lethal dose of TCDD, it is probable that this earlier disturbance of glucose metabolism is part of the biological changes that result in wasting away and eventually in death.

ISSN:0098-4108    

DOI:10.1080/15287398709531063

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Dermal penetration of carbofuran was determined in young (33 d) and adult (82 d) female Fischer 344 rats employing in vivo and in vitro methods. in vivo dermal penetration at 120 h was 43% for young and 18% for adult rats. The half‐time for carbofuran skin penetration (in vivo) was 128 h for the young and 400 h for the adults. The young to adult ratio of dermal penetration was greater than 1 at all time points (average 2.9) and had a maximum of 4.2 at 24 h. Cumulative urinary excretion approached about 95% of the absorbed dose in both the young and adult animals at 120 h. Whole‐body retention was slightly higher in adults. Kidney showed the highest tissue‐to‐blood concentration ratio (4.6 in adult, 2.3 in young). The ratio for the carcass was 2.8 in the adult and 2.4 in the young. The urine/blood concentration ratio was high, 435 in the adult and 573 in the young. The feces/blood ratio was 44 in the adult and 65 in the young. Skin absorption by the in vitro continuous‐flow system was 41% for the young and 11% for the adult at 72 h, compared to 36% and 13% by the in vivo method. The static in vitro method gave consistently lower skin penetration values of 12% for the young and 8.8% for the adult. Differences in the kinetics of retention and excretion were observed between the young and adult animals.

ISSN:0098-4108    

DOI:10.1080/15287398709531064

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor

摘要:

Dichloromethane extracts of four diverse hazardous wastes (coke plant, herbicide manufacturing, pulp and paper, and oil refining) were evaluated for mutagenicity in strains TA98 and TA100 of Salmonella. These extracts also were tested for biological activity in short‐term mammalian cell assays, including mutagenicity in L5178Y/TK+1mouse lymphoma cells, chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary (CHO) cells, morphological transformation in BALB/c‐3T3 cells, and teratogenic potential in mouse limb bud cells. The mammalian cell assays were performed using limited protocols that consisted of a preliminary testing of the extracts for cytotoxicity in CHO cells in order to estimate the appropriate dose range for the other assays. These assays were then performed once with only a few doses of extract; all but the mouse limb bud assay were performed in the presence of metabolic activation. Although all four of the wastes were presumptively positive for either mutation or cytogenetic effects, none of the wastes transformed BALB/C‐3T3 cells. Further studies are needed to establish which mammalian cell assays, if any, might be useful complements to the Salmonella assay for the purpose of screening hazardous wastes.

ISSN:0098-4108    

DOI:10.1080/15287398709531065

出版商:Taylor & Francis Group    

年代:1987

数据来源: Taylor