Screen clipping taken: 3/8/2015, 9:33 PMToksisitas jangka panjang dan studi carcinogenicity dari siklamat pada primata bukan manusia.Dua puluh satu monyet (cynomolgus, rhesus, hijau Afrika) diberi makan siklamat (100 mg / kg dan 500 mg / kg) dalam diet lima kali per minggu dari beberapa hari setelah lahir dan berlanjut sampai 24 tahun. Tumor ganas didiagnosis dalam tiga monyet siklamat 24 tahun; ini adalah usus karsinoma metastatik (rhesus, 500 mg / kg), karsinoma hepatoseluler metastatik (cynomolgus; 500 mg / kg), dan kecil, adenokarsinoma juga dibedakan dari prostat (cynomolgus; 100 mg / kg). Tumor jinak ditemukan di nekropsi dalam tiga perempuan; ini adalah adenoma kelenjar tiroid (rhesus, 100 mg / kg) dan dua kasus leiomyoma rahim (rhesus, 100 mg / kg dan 500 mg / kg). Tidak ada tumor terdeteksi dalam kelompok kontrol dengan usia yang sama dari 16 monyet. Pemeriksaan testis mengungkapkan atrofi testis lengkap di salah satu monyet siklamat tua, dan fokus aplasia sel germinal (tubulus Sertoli-satunya) dalam dua monyet siklamat lainnya. Gangguan spermatogenik focal (penangkapan pematangan) pada berbagai tingkat sel germinal dicampur dengan spermatogenesis normal diamati di kedua siklamat diobati dan kontrol monyet, yang semuanya berusia lebih dari 20 tahun. Pengukuran konsentrasi cyclohexylamine terminal menunjukkan bahwa tiga dari laki-laki tertutup dengan siklamat pada 500 mg / kg adalah konverter tinggi, dengan konsentrasi plasma sebanding dengan tingkat yang menghasilkan atrofi testis pada tikus. Namun, hanya satu dari tiga konverter tinggi menunjukkan bukti histologis spermatogenesis tidak teratur. Kesimpulan keseluruhan adalah bahwa kelainan testis dan kasus sporadis keganasan yang berbeda ditemukan setelah lebih dari 20 tahun dosis tidak memberikan bukti yang jelas tentang efek toksik atau karsinogenik natrium siklamat pada monyet.

Screen clipping taken: 3/8/2015, 9:39 PMEfek dari lima pemanis buatan pada Caco-2, HT-29 dan HEK-293 sel.van Eyk AD1.Penulis Informasi1Division Farmakologi, Departemen Farmasi dan Farmakologi, Universitas Witwatersrand, Parktown, Afrika Selatan.AbstrakAbstrak Konteks: Pemanis buatan (AS) telah dikaitkan dengan perkembangan tumor (termasuk kanker usus besar) di kedua hewan dan manusia meskipun bukti telah bertentangan. Tujuan: Penelitian tambahan demikian dilakukan dengan mempelajari efek dari 5 AS pada morfologi, proliferasi sel dan DNA dalam sel dengan memanfaatkan garis sel Caco-2, HT-29 (kolon) dan HEK-293 (ginjal). Bahan dan metode: Sel terkena natrium siklamat, sakarin natrium, sucralose dan acesulfame-K (0-50 mM) dan aspartame (0-35 mM) lebih dari 24, 48 dan 72 jam. Perubahan morfologi disajikan fotografi dan viabilitas sel% ditentukan dengan menggunakan viabilitas sel assay MTT. Kemungkinan kerusakan DNA (uji komet) yang disebabkan oleh AS (0,1, 1 dan 10 mM, dirawat selama 24, 48 dan 72 jam) dipelajari. Munculnya "komet" itu mencetak gol dari tidak ada kerusakan kerusakan parah (0-4). Hasil: Sel menjadi datar dan kurang baik didefinisikan pada tinggi AS konsentrasi (> 10 mM). Pada konsentrasi> 10 mM, penurunan viabilitas sel tercatat dengan baik meningkatkan konsentrasi dan meningkatkan waktu inkubasi untuk semua lini sel diuji. Secara umum, HEK-293 sel tampaknya kurang terpengaruh maka sel-sel kanker usus besar. Sucralose dan natrium sakarin tampaknya untuk memperoleh tingkat terbesar fragmentasi DNA dari semua pemanis diuji di semua lini sel digunakan. Diskusi: perubahan sel morfologi, viabilitas sel dan fragmentasi DNA tampaknya lebih dalam sel-sel kanker usus besar. Kesimpulan: Penelitian lebih lanjut harus dilakukan untuk memperjelas mekanisme yang terlibat menyebabkan perubahan ini dalam sel mamalia.

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Screen clipping taken: 3/8/2015, 9:44 PMEffects of a saccharin andcyclamatemixture on rat embryos.Damasceno DC1,Goncalves MA,Durante LC,Castro NC,Moura CH,Oliveira CB.Author informationAbstractSodium saccharin (NaS) and calciumcyclamate(CaC) are artificial sweeteners widely used in food and drink. To evaluate their toxicological effects on preimplantation mammalian embryos, pregnant rats were gavaged with 1.65 mg NaS/kg bw + 3.85 mg CaC/kg bw (DI) or 6.6 mg NaS/kg bw + 15.4 mg CaC/kg bw (D2) on days 1, 2, 3 and 4 of pregnancy (positive vaginal smear = day 1). The female rats were killed on day 5 of the pregnancy (GD 5), maternal organs weighed, and the blastocysts collected, counted and evaluated for gross morphology, cell number and mitotic index. There was no alteration in maternal organ weights, but there was an increase of the cell number/embryo in the dams treated with that NaS + CaC mixtures (D1 = 37.20 +/- 7.96; D2 = 37.26 +/- 10.90) compared to control group (32.24 +/- 6.73). Embryos whose dams were exposed to NaS + CaC may have adapted for implantation into the uterus but more studies are needed to demonstrate this mechanism of action.PMID:12776796[PubMed - indexed for MEDLINE]Pasted from In Vivo.2000 Jan-Feb;14(1):149-56.Susceptibility of nonhuman primates to carcinogens of human relevance.Schoeffner DJ1,Thorgeirsson UP.Author informationAbstractNonhuman primates are a valuable experimental model for the evaluation of human carcinogenic risk but have not been widely used for various reasons, such as high cost and lack of availability. The present review discusses the findings from a long-term carcinogenesis study in nonhuman primates that was carried out under contract by the National Cancer Institute from 1961 to 1997. Among the classes of compounds investigated were model rodent carcinogens, food additives, food and environmental contaminants, heterocyclic amines, N-nitroso compounds, and antineoplastic and immunosuppressives. Of the model rodent carcinogens tested, only urethane was carcinogenic in monkeys. Long-term administration of saccharin orcyclamatedid not result intoxicityor carcinogenicity in nonhuman primates, which is commonly seen in rodent models. Similar to rodent models and suspected in the human population, the fungal toxins, aflatoxin B1 and sterimatocystin, induced malignant liver tumors in monkeys. Relatively few animals administered DDT developed malignant tumors, however, hepatic and CNStoxicitywas commonly observed. Hepatocellular carcinoma developed in a majority of monkeys administered the heterocyclic amine, IQ but not the structurally similar MeIQx. Resultanttoxicityand carcinogenicity from N-nitroso compounds was variable. While diethylnitrosamine proved to be the most potent hepatocarcinogen tested, no malignant tumors were seen in animals administered N-methyl-N-nitro-N-nitrosoquanidine. Susceptibility of nonhuman primates to chemotherapeutic agents was also variable. Only procarbazine and N-methyl-N-nitrosourea were highly carcinogenic, whereas few tumors were seen as a result of cyclophosphamide, Adriamycin, melphalan, or azathioprine.PMID:10757072[PubMed - indexed for MEDLINE]Pasted from Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repair assay.Jeffrey AM1,Williams GM.Author informationAbstractThe non-nutritive sweeteners acesulfame-K, aspartame,cyclamate, saccharin and sucralose were tested for DNA damaging activity in the rat hepatocyte/DNA repair assay. Using hepatocytes from F344 and Sprague-Dawley male rats, all were inactive despite strong responses for the positive control, 2-aminofluorene.PMID:10722887[PubMed - indexed for MEDLINE]Pasted from Fetal mouse salivary glands and applications for determining teratogenic mechanisms in vitro.Lyng RD1.Author informationAbstractCulture systems offer advantages for studying the actions of chemicals on mechanisms of development. Growth, [3H]thymidine incorporation, and 14C-amino acid incorporation were measured to determine culture conditions and the response of glands to three chemicals. Eagle's MEM supported the best growth and the best time for double isotope presence was the second 24 h of culture.Cyclamatehad no effect on growth or isotope incorporation but cycloheximide disturbed 14C more than 3H. 5-Azacytidine was toxic but the incorporation of both isotopes exhibited the same pattern.PMID:1283233[PubMed - indexed for MEDLINE]Pasted from Crit Rev Toxicol.1992;22(2):81-118.Assessment of the carcinogenicity of the nonnutritive sweetenercyclamate.Ahmed FE1,Thomas DB.Author informationAbstractThe weight of the evidence from metabolic studies, short-term tests, animal bioassays, and epidemiological studies indicates thatcyclamate(CHS) is not carcinogenic by itself; however, there is evidence from in vitro and in vivo studies in animals that implies it may have cancer-promoting or cocarcinogenic activity. Epidemiological studies indicate that the use of nonnutritive sweeteners (CHS and saccharin) has not resulted in a measurable overall increase in the risk of bladder cancer in individuals who have ever used these products. No epidemiological information exists on the possible associations of these sweeteners and cancers other than those of the urinary tract. It is recommended that (1) no further studies on the metabolism of CHS to evaluate its carcinogenicity are required since no potentially hazardous metabolites have been appreciably detected in humans; (2) no further animal bioassays to test for the carcinogenicity of CHS by itself are necessary; (3) the studies in rodents that suggest a promotional or cocarcinogenic effect of CHS should be repeated because they cannot be ruled out; (4) because the significance to human health of a positive outcome of such studies is uncertain, additional research aimed at understanding the predictive value for human health of such results and more generic studies to develop well-validated systems that can be relied on in the assessment of cancer-promoting agents are recommended; (5) in populations where CHS continues to be used, epidemiological monitoring should be continued to determine whether there is an increased risk of cancer in humans who are heavy or long-term users or for those observed long after first exposure. In such monitoring, other cancer sites--in addition to the bladder--should be considered.PMID:1510820[PubMed - indexed for MEDLINE]Pasted from AbstractSend to:Int JCancer.1988 Aug 15;42(2):295-8.Effects of sodiumcyclamateand sodium saccharin on focus induction in explant cultures of rat bladder.Nicholson LJ1,Jani H.Author informationAbstractThe tumour-promoting activities of sodiumcyclamateand sodium saccharin were investigated in an assay based on the induction of epithelial foci exhibiting enhanced growth potential in a rat bladder explant culture system. An initiating, non-focus-inducing dose was defined for the carcinogen N-methyl-N-nitrosourea (MNU) to make promotion studies possible. Saccharin induced epithelial foci when added to cultures pretreated with an initiating dose of MNU, and also increased the incidence of foci in cultures treated with transforming doses of MNU.Cyclamatewas found to induce a high incidence of foci when added to cultures by itself. When MNU andcyclamatetreatments were combined, an additive effect could be detected. These results indicate that bothcyclamateand saccharin can contribute to epithelial transformation in this system.