Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay...Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay system. The natural retinoids included all-trans-retinoic (RA), 13-cis-retinoic acid, 4-oxoretinoic acid, and retinol. Among the synthetic retinoids tested were all trans N-(4-hydroxy(phenyl)retinamide, 3-substituted oxoretinoic acids, and 13 cis-N-ethylretinamide. The animal models employed were: 1) vitamin A-deficient hamster tracheal organ assay (HTOC);2) the benzo(α)pyrene-induced squamous metaplasia in a hamster tracheal organ system (BP-HTOC);3) the mouse skin tumor promoter (TPA)-induced ornithine decarboxylase enzyme assay(ODC);4) the mouse skin papilloma (MPA) assay;and 5) a novel retinoid bioassay in which retinoids display IC<sub>50</sub> values to inhibit clonal growth of NHK. All-trans-RA, 4-oxoretinoic acid and retinol were consistently more active than any of the synthetic derivatives in all bioassays tested. A statistical model was developed and significant positive correlations were found between: 1) ED<sub>50</sub> values in the HTOC system and reduction in TPA-induced ODC enzyme activity;2) tumors per animal in the MPA bioassay and suppression of TPA-induced ODC activity;and 3) a positive correlation between suppression of tumors per animal in the MPA assay, and retinoid inhibition of keratinocyte clonal growth. Test retinoids, were tested for their capacity to inhibit the clonal growth of a squamous carcinoma cell line (SCC-25), which were found to be 2 - 3 logs less sensitive for each tested retinoid than the corresponding activity against NHK cells. Antineoplastic retinoid drugs were reviewed.展开更多
Study on effective disposal and utilization of sewage sludge has recently been the target of growing interest in China. However, potential risks are associated with the use of sludge due to its contamination with toxi...Study on effective disposal and utilization of sewage sludge has recently been the target of growing interest in China. However, potential risks are associated with the use of sludge due to its contamination with toxic organics, heavy metals and pathogenic microorganisms. In this study, a screening assessment was conducted on sewage sludge samples collected from 17 different sewage treatment plants in Beijing, based on a batch of in vitro bioassays, including a set of recombinant gene yeast assays for endocrine disruption, and an ethoxy resorufin-O- deethylase （EROD） assay using H4IIE cells for aryl hydrocarbon receptor （Ah-R） agonistic activities. Our results suggested that moderate levels of estrogen receptor agonistic activities （0.9 ng E2. g-1 to 6.8 ng E2. gl, dw）, but relative higher androgen receptor antagonistic activ- ities （nd to 45%）, progestin receptor antagonistic activities （nd to 80%） and Ah-R agonistic activities （1390 to 6740 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD）·g-1, dw） were found in sewage sludge samples. However, there were no significant correlations between the toxic effects of sewage sludge and the sewage treatment processes. In addition, the 17β-estradiol （E2） equivalent quantity （EEQ） level of the sewage sludge was increased after the composting treatment, whereas the 2,3,7,8-tetrachlorodi- benzo-p-dioxin toxic equivalent quantity （TEQ） level of sewagesludge composted was much lower than that of sewage sludge.展开更多
In the race to deliver clean water to communities through potable water reuse, disinfection and water quality assessment are and will continue to be fundamental factors. There are over 700 disinfection byproducts(DBPs...In the race to deliver clean water to communities through potable water reuse, disinfection and water quality assessment are and will continue to be fundamental factors. There are over 700 disinfection byproducts(DBPs) in water;evaluating each compound is practically impossible and very time consuming. A bioanalytical approach could be an answer to this challenge. In this work, the response of four major classes of DBPs toward mitochondrial membrane potential( Δψm) and cytoplasmic adenosine triphosphate(C-ATP) was investigated with human carcinoma(Hep G2) cells. Within 90 min of cell exposure, only the haloacetic acid(HAA) mixture caused a cytotoxic response as measured by C-ATP. All four groups(haloacetonitriles(HANs), trihalomethanes(THMs), nitrosamines(NOAs), and HAAs) responded well to Δψm, R 2 > 0.70. Based on the half-maximum concentration that evoked a 50% response in Δψm, the response gradient was HANs >> HAAs ~ THM > NOAs. The inhibition of the Δψm by HANs is driven by dibromoacetonitrile(DBAN), while dichloroacetonitrile(DCAN) did not cause a significant change in the Δψm at less than 2000 μM. A mixture of HANs exhibited an antagonistic behavior on the Δψm compared to individual compounds. If water samples are concentrated to increase HAN concentrations, especially DBAN, then Δψm could be used as a biomonitoring tool for DBP toxicity.展开更多
文摘Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay system. The natural retinoids included all-trans-retinoic (RA), 13-cis-retinoic acid, 4-oxoretinoic acid, and retinol. Among the synthetic retinoids tested were all trans N-(4-hydroxy(phenyl)retinamide, 3-substituted oxoretinoic acids, and 13 cis-N-ethylretinamide. The animal models employed were: 1) vitamin A-deficient hamster tracheal organ assay (HTOC);2) the benzo(α)pyrene-induced squamous metaplasia in a hamster tracheal organ system (BP-HTOC);3) the mouse skin tumor promoter (TPA)-induced ornithine decarboxylase enzyme assay(ODC);4) the mouse skin papilloma (MPA) assay;and 5) a novel retinoid bioassay in which retinoids display IC<sub>50</sub> values to inhibit clonal growth of NHK. All-trans-RA, 4-oxoretinoic acid and retinol were consistently more active than any of the synthetic derivatives in all bioassays tested. A statistical model was developed and significant positive correlations were found between: 1) ED<sub>50</sub> values in the HTOC system and reduction in TPA-induced ODC enzyme activity;2) tumors per animal in the MPA bioassay and suppression of TPA-induced ODC activity;and 3) a positive correlation between suppression of tumors per animal in the MPA assay, and retinoid inhibition of keratinocyte clonal growth. Test retinoids, were tested for their capacity to inhibit the clonal growth of a squamous carcinoma cell line (SCC-25), which were found to be 2 - 3 logs less sensitive for each tested retinoid than the corresponding activity against NHK cells. Antineoplastic retinoid drugs were reviewed.
文摘Study on effective disposal and utilization of sewage sludge has recently been the target of growing interest in China. However, potential risks are associated with the use of sludge due to its contamination with toxic organics, heavy metals and pathogenic microorganisms. In this study, a screening assessment was conducted on sewage sludge samples collected from 17 different sewage treatment plants in Beijing, based on a batch of in vitro bioassays, including a set of recombinant gene yeast assays for endocrine disruption, and an ethoxy resorufin-O- deethylase （EROD） assay using H4IIE cells for aryl hydrocarbon receptor （Ah-R） agonistic activities. Our results suggested that moderate levels of estrogen receptor agonistic activities （0.9 ng E2. g-1 to 6.8 ng E2. gl, dw）, but relative higher androgen receptor antagonistic activ- ities （nd to 45%）, progestin receptor antagonistic activities （nd to 80%） and Ah-R agonistic activities （1390 to 6740 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD）·g-1, dw） were found in sewage sludge samples. However, there were no significant correlations between the toxic effects of sewage sludge and the sewage treatment processes. In addition, the 17β-estradiol （E2） equivalent quantity （EEQ） level of the sewage sludge was increased after the composting treatment, whereas the 2,3,7,8-tetrachlorodi- benzo-p-dioxin toxic equivalent quantity （TEQ） level of sewagesludge composted was much lower than that of sewage sludge.
基金supported by the National Science Foundation (No. 1833108)。
文摘In the race to deliver clean water to communities through potable water reuse, disinfection and water quality assessment are and will continue to be fundamental factors. There are over 700 disinfection byproducts(DBPs) in water;evaluating each compound is practically impossible and very time consuming. A bioanalytical approach could be an answer to this challenge. In this work, the response of four major classes of DBPs toward mitochondrial membrane potential( Δψm) and cytoplasmic adenosine triphosphate(C-ATP) was investigated with human carcinoma(Hep G2) cells. Within 90 min of cell exposure, only the haloacetic acid(HAA) mixture caused a cytotoxic response as measured by C-ATP. All four groups(haloacetonitriles(HANs), trihalomethanes(THMs), nitrosamines(NOAs), and HAAs) responded well to Δψm, R 2 > 0.70. Based on the half-maximum concentration that evoked a 50% response in Δψm, the response gradient was HANs >> HAAs ~ THM > NOAs. The inhibition of the Δψm by HANs is driven by dibromoacetonitrile(DBAN), while dichloroacetonitrile(DCAN) did not cause a significant change in the Δψm at less than 2000 μM. A mixture of HANs exhibited an antagonistic behavior on the Δψm compared to individual compounds. If water samples are concentrated to increase HAN concentrations, especially DBAN, then Δψm could be used as a biomonitoring tool for DBP toxicity.
