An evaluation of the cho/hgprt mutation assay involving suspension cultures and soft agar cloning: Results for 33 chemicals

At baseline, the EQ-5D scores were highly correlated with the HAQ (r ‫؍‬ ؊0.74) and moderately correlated with the DAS28 (r ‫؍‬ ؊0.47), whereas the TTO correlated poorly with both the HAQ and DAS28. Correlation between the mean change in the EQ-5D and in the HAQ was moderate (r ‫؍‬ ؊0.55). Conclusion. TTO and EQ-5D do not yield the same utility values. The results suggest that the EQ-5D is more representative of RA status than the TTO, a valuable conclusion when addressing economic evaluations in RA.

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“… See Ref. 35 for further details on negative results in a mutation assay involving suspension cultures and soft agar cloning. …”

Section: Results Of Calculationsmentioning

confidence: 99%

Assessing utility values in rheumatoid arthritis: A comparison between time trade‐off and the EuroQol

Ariza‐Ariza

Hernández‐Cruz

Carmona

et al. 2006

Arthritis & Rheumatism

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“…However, aromatic polycyclic hydrocarbons are not genotoxic in most test systems (24,25), including Chinese hamster cells in vitro-unless oxidized by liver enzymes (21,70). Outside the liver they persist even in animals metabolically unchanged for weeks and months (83)(84)(85).…”

Section: Discussionmentioning

confidence: 99%

“…To minimize transformation by gene mutation, we have used the aromatic polycyclic hydrocarbons benzo[a]pyrene (BP), methylcholanthrene (MCA), dimethylbenzanthracene (DMBA), which are nongenotoxic in CHE cells unless oxidized by liver enzymes (21,25,70) and colcemid (54).…”

mentioning

confidence: 99%

Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells

Yerganian

Duesberg

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

162

111

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Aneuploidy or chromosome imbalance is the most massive genetic abnormality of cancer cells. It used to be considered the cause of cancer when it was discovered more than 100 years ago. Since the discovery of the gene, the aneuploidy hypothesis has lost ground to the hypothesis that mutation of cellular genes causes cancer. According to this hypothesis, cancers are diploid and aneuploidy is secondary or nonessential. Here we reexamine the aneuploidy hypothesis in view of the fact that nearly all solid cancers are aneuploid, that many carcinogens are nongenotoxic, and that mutated genes from cancer cells do not transform diploid human or animal cells. By regrouping the gene pool-as in speciation-aneuploidy inevitably will alter many genetic programs. This genetic revolution can explain the numerous unique properties of cancer cells, such as invasiveness, dedifferentiation, distinct morphology, and specific surface antigens, much better than gene mutation, which is limited by the conservation of the existing chromosome structure. To determine whether aneuploidy is a cause or a consequence of transformation, we have analyzed the chromosomes of Chinese hamster embryo (CHE) cells transformed in vitro. This system allows (i) detection of transformation within 2 months and thus about 5 months sooner than carcinogenesis and (ii) the generation of many more transformants per cost than carcinogenesis. To minimize mutation of cellular genes, we have used nongenotoxic carcinogens. It was found that 44 out of 44 colonies of CHE cells transformed by benz[a]pyrene, methylcholanthrene, dimethylbenzanthracene, and colcemid, or spontaneously were between 50 and 100% aneuploid. Thus, aneuploidy originated with transformation. Two of two chemically transformed colonies tested were tumorigenic 2 months after inoculation into hamsters. The cells of transformed colonies were heterogeneous in chromosome number, consistent with the hypothesis that aneuploidy can perpetually destabilize the chromosome number because it unbalances the elements of the mitotic apparatus. Considering that all 44 transformed colonies analyzed were aneuploid, and the early association between aneuploidy, transformation, and tumorigenicity, we conclude that aneuploidy is the cause rather than a consequence of transformation.

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“…At these fluoride levels in the medium growth and survival of cells were also reduced. Sodium fluoride (200-500 μg/mL) did not increase the frequency of mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in various cell systems exposed under neutral or acidic conditions (Oberly et al, 1990;Slamenova et al, 1992;1996).…”

Section: In Vitro Studiesmentioning

confidence: 93%

Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies (NDA) on a request from the Commission related to the Tolerable Upper Intake Level of Fluoride

Products¹

2005

EFSA Journal

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SUMMARYFluoride is not essential for human growth and development but is beneficial in the prevention of dental caries (tooth decay) when ingested in amounts of about 0.05 mg/kg body weight per day and when applied topically with dental products such as toothpaste. Dental enamel which contains fluoride is less likely to develop caries, because of greater resistance to ingested acids or to acids generated from ingested sugars by the oral bacteria. In addition, fluoride inhibits sugar metabolism by oral bacteria.Fluoride content of the body is not under physiological control. Absorbed fluoride is partly retained in bone and partly excreted, predominantly via the kidney. In infants retention in bone can be as high as 90% of the absorbed amount, whereas in adults retention is 50% or less. Fluoride is also incorporated into dental enamel during tooth formation.Excessive intake of fluoride during enamel maturation before tooth eruption from birth to eight years of age, when enamel formation is complete, can lead to reduced mineral content of enamel and to dental fluorosis of deciduous but predominantly of permanent teeth. The incidence and severity of dental fluorosis is dose-dependent. Mild dental fluorosis is not readily apparent and is associated with increased resistance to caries. The Panel considered moderate dental fluorosis, which is characterised by staining and minute pitting of teeth, to be an adverse effect. On the basis that the prevalence of moderate dental fluorosis of permanent teeth is less than 5% in populations ingesting 0.08-0.12 mg fluoride/kg body weight/day, the Panel considered that the upper level (UL) for fluoride is 0.1 mg fluoride/kg/day in children aged 1-8 years. This is equivalent to 1.5 and 2.5 mg fluoride per day in children aged 1-3 years and 4-8 years, respectively.Fluoride accretion in bone increases bone density but excessive long term intake reduces bone strength and increases risk of fracture and skeletal fluorosis (stiffness of joints, skeletal deformities). Studies with therapeutic oral administration of fluoride in amounts of 0.6 mg/kg body weight/day in postmenopausal women over several years increased the risk for nonvertebral bone fractures significantly. The Panel applied an uncertainty factor of 5 to derive an UL of 0.12 mg/kg body weight/day. This is equivalent to an UL of 5 mg/day in children aged 9-14 years and 7 mg/day for age 15 years and older, including pregnant and lactating women.The UL for fluoride applies to intake from water, beverages, foodstuffs, including fluoridated salt, dental health products and fluoride tablets for caries prevention.Children aged 1-8 years have fluoride intakes from food and water well below the UL provided the fluoride content of their drinking water is not higher than 1.0 mg/L. An increase

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An evaluation of the cho/hgprt mutation assay involving suspension cultures and soft agar cloning: Results for 33 chemicals

Cited by 33 publications

References 18 publications

Assessing utility values in rheumatoid arthritis: A comparison between time trade‐off and the EuroQol

Assessing utility values in rheumatoid arthritis: A comparison between time trade‐off and the EuroQol

Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells

Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies (NDA) on a request from the Commission related to the Tolerable Upper Intake Level of Fluoride

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