Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells

Lindahl-Kiessling, Kerstin; Karlberg, Inger; Olofsson, Anne-Mari

doi:10.1016/0027-5107(89)90108-5

Cited by 19 publications

(10 citation statements)

References 26 publications

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“…However, at a dose below that which increased doubling time, single chromatid aberrations and sister chromatid aberrations were increased in lymphocytes from a single donor after DEHP incubation [194]. Unlike mammalian cell lines, human peripheral lymphocytes from differing donors do not react identically [116]. Stenchever et al [182] reported the significance of chromosome breaks and gaps only after combination between a few donors with highly variable responses.…”

Section: Mg/ml)mentioning

confidence: 92%

“…In addition, the reversal of DEHP-induced DNA damage to human leukocytes has been reported from S-9 addition [13,146]. Lindahl-Kiessling et al [116] noted that S-9 mix cannot replace metabolic activation by hepatocytes in lymphocytic cultures since the co-factors necessary for S-9 mix inhibit DNA synthesis strongly (i.e., NADPH, NADP and G-6-P being responsible for the effect). They also noted that cocultures of lymphocytes and hepatocytes require differing optimal conditions for survival.…”

Section: Mg/ml)mentioning

confidence: 95%

“…chromosomal aberrations, micronuclei, aneuploidy) and DNA strand breaks Human data on DEHP-or MEHP-induced chromosomal effects and DNA strand breaks are presented in Table 1. With the exception of the Lindahl-Kiessling et al [116] study, sister chromatid exchange (SCE) and chromosomal aberration assays of human lymphocytes treated in vitro with DEHP have mostly reported negative results using the highest ineffective dose [146,182,194]. However, negative conclusions from these studies are confounded by several factors including use of exposure concentrations that exceed solubility [146] and lack of dose response due to inhibition of lymphocyte growth [194].…”

Section: Mg/ml)mentioning

confidence: 98%

“…Increased induction of human lymphocyte SCE was reported at levels below causing DEHP precipitation with and without coculture of rat hepatocytes separated from human lymphocytes [116]. In this paradigm, the rat hepatocytes were separated from human lymphocytes with a lower DEHP concentration inducing SCE than lymphocytes alone.…”

Section: Mg/ml)mentioning

confidence: 98%

See 3 more Smart Citations

DEHP: Genotoxicity and potential carcinogenic mechanisms—A review

Caldwell

2012

Mutation Research/Reviews in Mutation Research

193

101

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Section: Mg/ml)mentioning

confidence: 92%

Section: Mg/ml)mentioning

confidence: 95%

Section: Mg/ml)mentioning

confidence: 98%

Section: Mg/ml)mentioning

confidence: 98%

See 2 more Smart Citations

DEHP: Genotoxicity and potential carcinogenic mechanisms—A review

Caldwell

2012

Mutation Research/Reviews in Mutation Research

193

101

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“…This experiment was carried out by a variation of the method for cocultivation of cells (Lindahl-Kiessling et al 1989). Similar methods have been described earlier (San and Williams 1977;Brat and Williams 1982).…”

Section: Coculture Of Human Lymphocytes and Hepg2 Cells Human Hepatomamentioning

confidence: 99%

On the bioactivation and genotoxic action of fluoranthene

et al. 1992

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Fluoranthene (FA) was studied with respect to possible mechanisms of its high mutagenicity but low carcinogenicity, in comparison with the corresponding properties of benzo[a]pyrene (BaP), and with regard to the synergism of these two compounds shown by van Duuren and Goldschmidt (J Natl Cancer Inst 56, 1976, 1237). FA and BaP activated by S9 from Aroclor 1254 (PCB)-treated rats induce HPRT mutations in CHO cells with about equal effectiveness at the same exposure doses, which also lead to the same frequencies of repairable DNA adducts, enzyme-induced strand breaks being used as an indirect measure of adducts to DNA. FA was also shown to be an efficient inducer of SCE in human peripheral lymphocytes cocultivated with PCB-treated HepG2 cells or with liver cells from PCB-pretreated rats. For the induction of SCE, FA and BaP were shown to act additively. From metabolic studies with liver microsomes from C57Bl/6 mice it is concluded that, whereas BaP induces the metabolism of BaP to the mutagenic epoxide, neither BaP nor FA is able to induce the metabolism of FA. In mutation experiments with V79 cells (XEM2) constitutive for P450 IA1 activity, BaP 7,8-diol but not FA 2,3-diol provokes a high frequency of HPRT mutations. In cells constitutive for P450 IA2 enzymatic activity FA and BaP are but weakly mutagenic and practically nonmutagenic, respectively. Due to the additivity of the genotoxic effects of FA and BaP, induction of an error-prone condition by the latter compound seems to be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

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Di(2‐ethylhexyl)phthalat (DEHP) [MAK Value Documentation in German language, 2002]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 35. Lieferung, Ausgabe 2002 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Rezeptor‐vermittelte Mechanismen Rezeptor‐unabhängige Mechanismen Zusammenfassende Betrachtung der verschiedenen Mechanismen Toxikokinetik und Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhaut Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Bewertungen

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Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells

Cited by 19 publications

References 26 publications

DEHP: Genotoxicity and potential carcinogenic mechanisms—A review

DEHP: Genotoxicity and potential carcinogenic mechanisms—A review

On the bioactivation and genotoxic action of fluoranthene

Di(2‐ethylhexyl)phthalat (DEHP) [MAK Value Documentation in German language, 2002]

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