Human exposure to mutagenic/carcinogenic heterocyclic amines and comutagenic β-carbolines

Wakabayashi, Keiji; Totsuka, Yukari; Fukutome, Kazuo; Oguri, Atsuko; Ushiyama, Hirofumi; Sügimura, Takashi

doi:10.1016/s0027-5107(97)00050-x

Cited by 73 publications

(29 citation statements)

References 19 publications

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“…Similarly, β-carboline alkaloids produce toxic damage with significant loss of cerebellar Purkinje cells (Du et al, 1997;Milner et al, 1995;O'Hearn and Molliver, 1997;Robertson, 1980;Sinton et al, 1989). While β-carboline alkaloids are produced endogenously in the human body (Gearhart et al, 2000;Wakabayashi et al, 1997), one study estimated that dietary sources were fifty times greater than endogenous sources (Pfau and Skog, 2004). β-carboline alkaloids are primarily found in muscle foods (beef, chicken, pork, fish) at ng/g concentrations and cooking leads to increased concentrations (Gross et al, 1993;Layton et al, 1995;Skog, 1993;Skog et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Louis

2008

NeuroToxicology

127

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Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3 ± 15.5 vs. 65.5 ± 14.2 years, p = 0.94). Mean log blood harmane concentration was ∼50% higher in cases than controls (0.50 ± 0.54 g -10 /ml vs. 0.35 ± 0.62 g -10 /ml, p = 0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (OR adjusted 1.56, 95% CI 1.01 -2.42, p = 0.04), and odds of ET was 1.90 (95% CI 1.07 -3.39, p = 0.029) in the highest vs. lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53 ± 0.57 g -10 /ml), intermediate in cases with sporadic ET (0.43 ± 0.45 g -10 /ml) and lowest in controls (0.35 ± 0.62 g -10 /ml) (test for trend, p = 0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors.

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Section: Discussionmentioning

confidence: 99%

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Louis

2008

NeuroToxicology

127

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“…The similarities in design of the longer and the short versions of the questionnaire may cause an overestimated validity of the short version 41 . No gold standard exists to validate an HCA questionnaire, since measurements of DNA-adducts 45,46 or excreted HCA metabolites in urine 47,48 are either not sensitive enough or have other limitations. An appropriate way could be the double portion technique, where a part of the food consumed is analysed for its HCA content, but this method is expensive and only useful in small groups of individuals.…”

Section: Discussionmentioning

confidence: 99%

Development of a short questionnaire to assess the dietary intake of heterocyclic aromatic amines

Rohrmann

Becker

2002

Public Health Nutr.

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Objective: Development and validation of a short instrument to assess the dietary intake of heterocyclic aromatic amines (HCA). Design: At first, a longer instrument asking for the consumption of 11 meat and fish items and different preparation methods was developed. The degree of browning of these foods was assessed by means of photos. This questionnaire was sent to 500 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg, Germany, in June 1999. Using 385 completed questionnaires, a short questionnaire was developed covering just seven food items, which was sent to the participants again. Of these, 344 were returned within four months. Total dietary intake of HCA as well as the intake of different HCA were calculated and compared between both versions. , respectively. These results did not differ significantly from those obtained with the longer version. Spearman rank correlation coefficients between the long and the short version ranged from 0.46 to 0.6. In quartile cross-classification, 70 -78% of the participants were assigned into the same or an adjacent quartile while categorisation into opposite quartiles was #3.5%. Conclusion: The short version of the HCA questionnaire demonstrates good validity compared with the longer version. The intake of HCA as assessed with the short questionnaire is comparable to that found in other studies using a short questionnaire.

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“…Human safety is assured if the SEL is greater than human exposure. Humans are not exposed to AAF, a synthetic compound, and humans are exposed to only traces of DEN (14), but the likely environmental exposure to all N-nitroso compounds and to aromatic amines is unlikely to exceed the NEL levels described here, except for the exposures of cigarette smokers, snuff users (24, 31), and individuals who consume exceptionally large quantities of foods that are rich in such compounds, such as some smoked meats and fish (32,38), or those exposed in occupational settings (37). …”

Section: Exposure-response Investigations Of Denmentioning

confidence: 99%

Mechanistic Basis for Nonlinearities and Thresholds in Rat Liver Carcinogenesis by the DNA-Reactive Carcinogens 2-Acetylaminofluorene and Diethylnitrosamine

2000

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To explore differences in mechanisms of carcinogenicity at low and high exposures, we have conducted a series of exposureresponse studies of hepatocarcinogenesis in rats using 2 well-studied DNA-reactive carcinogens, 2-acetylaminofluorene and diethylnitrosamine. In these studies, we have used intraperitoneal injection or intragastric instillation to deliver exact doses during an initiation segment followed by phenobarbital as a liver tumor promoter to enhance manifestation of initiation. This protocol results in carcinogenicity comparable to that produced by lifetime exposure to the carcinogens. Our

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Human exposure to mutagenic/carcinogenic heterocyclic amines and comutagenic β-carbolines

Cited by 73 publications

References 19 publications

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Development of a short questionnaire to assess the dietary intake of heterocyclic aromatic amines

Mechanistic Basis for Nonlinearities and Thresholds in Rat Liver Carcinogenesis by the DNA-Reactive Carcinogens 2-Acetylaminofluorene and Diethylnitrosamine

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