Formation of direct-acting genotoxic substances in nitrosated smoked fish and meat products: Identification of simple phenolic precursors and phenyldiazonium ions as reactive products

Ohshima, Hiroshi; Friesen, Marlin D.; Malaveille, Christian; Brouet, I.; Hautefeuille, A.; Bartsch, Helmut

doi:10.1016/0278-6915(89)90069-0

Cited by 99 publications

(44 citation statements)

References 21 publications

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“…32) Furthermore, reaction of catechol or phenol and nitrite produced o-benzoquinone and p-nitrosocatechol, and mutagenic diazonium compounds were produced after nitrosation under acidic conditions. 10,33) Therefore, in simultaneous administration of phenolic compounds, including HTHQ, and NaNO 2 , the production of these substances might have played a role in induction of cell proliferation and carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…5) On the other hand, it has been reported that mutagenic compounds were formed by the interaction of polyphenols with nitrite in vitro. 10,11) It was also reported that when several phenolic antioxidants such as catechol, hydroquinone, gallic acid, t-butylhydroquinone (TBHQ) or AsA and 0.2% NaNO 2 are simultaneously administered to rats, strong toxicity and cell proliferation are induced in the forestomach epithelium. Furthermore, continuous administration of AsA, sodium ascorbate, catechol or 3-methoxycatechol and 0.2-0.3% NaNO 2 for 24-51 weeks induced forestomach tumors, and also enhanced rat forestomach carcinogenesis initiated with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG).…”

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confidence: 99%

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Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

Yada

Hirose

Tamano³

et al. 2002

Japanese Journal of Cancer Research

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The effect of antioxidant, 0.25% 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) or 0.25% ascorbic acid (AsA), on carcinogenesis induced by administration of 0.05% aminopyrine (AP) and 0.05% sodium nitrite (NaNO 2 ), was examined using a rat multi-organ carcinogenesis model. Groups of twenty F344 male rats were treated sequentially with an initiation regimen of Ndiethylnitrosamine, N-methyl-N-nitrosourea, N-butyl-N-(4-hydroxybutyl)nitrosamine, N,N′ ′ ′ ′-dimethylhydrazine and 2,2′ ′ ′ ′-dihydroxy-di-n-propylnitrosamine during the first 4 weeks, followed by AP + + + +NaNO 2 , AP + + + +NaNO 2 + + + +HTHQ, AP + + + +NaNO 2 + + + +AsA, NaNO 2 + + + +HTHQ, NaNO 2 + + + +AsA, each of the individual chemicals alone or basal diet and tap water as a control. All surviving animals were killed at week 28, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. In the AP + + + +NaNO 2 group, the incidences of hepatocelluar adenomas and hemangiosarcomas were 95% and 35%, respectively. When HTHQ or AsA was simultaneously administered, the incidences decreased to 58% and 11%, or to 80% and 15%, respectively. On the other hand, in the AP + + + +NaNO 2 group and the NaNO 2 -alone group, when HTHQ, but not AsA, was simultaneously administered, the incidence of carcinomas in the forestomach significantly increased. The results suggest that HTHQ can prevent tumor production induced by AP and NaNO 2 more effectively than AsA. On the other hand, an enhancing or possible carcinogenic effect of simultaneous administration of HTHQ and NaNO 2 only on the forestomach is suggested, while simultaneous treatment with the same dose of AsA and NaNO 2 may not be carcinogenic to the forestomach or other organs.Key words: Antioxidants -Aminopyrine -Sodium nitrite -Carcinogenesis -RatMany nitrosoamines are known to induce tumors in various organs.1) It was reported that some drugs with secondary or tertiary amino groups reacted with nitrite under acidic conditions to form nitrosamines in vitro and in vivo. [2][3][4][5] In particular, aminopyrine (AP) is known to react with sodium nitrite (NaNO 2 ) to form dimethylnitrosamine (DMN), which is a potent liver, lung and renal carcinogen.2, 3, 6) Feeding of AP and NaNO 2 to rats has been shown to cause acute liver damage due to formation of DMN and eventually to cause liver tumors upon chronic treatment. 2,7,8) It is also known that ascorbic acid (AsA), and phenolic antioxidants such as caffeic acid, ferulic acid, butylated hydroxyanisole (BHA) and propyl gallate, inhibit the formation of DMN in rats receiving AP and NaNO 2 . 4,5) An inhibitory effect of caffeic acid on the endogenous formation of N-nitrosoproline was demonstrated in man. 9)Kuenzig et al. suggest that dietary phenols may play an important role in the prevention of carcinogenesis by inhibiting the formation of nitrosamines. 5)On the other hand, it has been reported that mutagenic compounds were formed by the interaction of polyphenols with nitrite in vitro.10, 11) It was also reported tha...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

Yada

Hirose

Tamano³

et al. 2002

Japanese Journal of Cancer Research

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“…Escherichia coli PQ37 5 mM (631 µg/ml) Negative Ohshima et al, 1989 The test system used is considered inappropriate, due to insufficient validity. …”

Section: Dna Damage (Sos Chromotest)mentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 213, Revision 2 (FGE.213Rev2): Consideration of genotoxic potential for α,β‐unsaturated alicyclic ketones and precursors from chemical subgroup 2.7 of FGE.19

Flavourings¹

2015

EFS2

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“…Phenylacetaldehyde .030] was tested in E. coli strain WP2uvrA/pKM101 with preincubation (Kato et al, 1989), and para-tolylacetaldehyde .042] was studied in E. coli strain PQ37 (Ohshima et al, 1989), both at unspecified concentrations. There was no evidence of mutagenicity in either assay.…”

Section: Genotoxicity Datamentioning

confidence: 99%

Flavouring Group Evaluation 53 (FGE.53): Consideration of phenethyl alcohol, aldehyde, acid and related acetals and esters evaluated by JECFA (59th meeting) structurally related to phenethyl alcohol, aldehyde, esters and related phenylacetic acid esters e

2008

EFSA Journal

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The present consideration concerns 41 phenylethyl alcohol, aldehyde, acid and related acetals and esters and related substances evaluated by the JECFA (59 th meeting) and will be considered in relation to the European Food Safety Authority (EFSA) evaluation of 10 phenethyl alcohol, aldehyde, esters and related phenylacetic acid esters evaluated in the Flavouring Group Evaluation 14 (FGE.14) and one phenoxyethyl ester evaluated in Flavouring Group Evaluation 23 (FGE.23).The Panel concluded that the 41 substances in the JECFA flavouring group of 41 phenylethyl alcohol, aldehyde, acid and related acetals and esters and related substances are structurally related to the group of ten phenethyl derivatives evaluated by EFSA in FGE.14 and one phenoxyethyl ester evaluated in FGE.23.Further two substances were evaluated by the JECFA in this group, which may be metabolised to alpha,beta-unsaturated aldehydes and will be considered together with other alpha,beta-unsaturated compounds.The Panel agrees with the application of the Procedure as performed by the JECFA for the 41 phenylethyl derivatives.For four substances 09.702, 09.783 and 16.041] the JECFA evaluation is only based on Maximised Survey-derived Daily Intake (MSDI) values derived from production figures from the USA. EU production figures are needed in order to finalise the evaluation of these substances.For all 41 substances evaluated through the Procedure use levels are needed to calculate the modified Theorical Added Maximum Daily Intake (mTAMDI) in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation.In order to determine whether the conclusion for the 41 JECFA evaluated substances can be applied to the materials of commerce, it is necessary to consider the available specifications: The EFSA Journal (2008) .................................................................................................................................... ...................................................................................................... ................................................................................................................................................................... 37 Scientific Panel Members............................................................................................................................................... 39 Acknowledgement......................................................................................................................................................

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Formation of direct-acting genotoxic substances in nitrosated smoked fish and meat products: Identification of simple phenolic precursors and phenyldiazonium ions as reactive products

Cited by 99 publications

References 21 publications

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

Effects of Antioxidant 1‐O‐Hexyl‐2,3,5‐trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi‐organ Carcinogenesis Model

Scientific Opinion on Flavouring Group Evaluation 213, Revision 2 (FGE.213Rev2): Consideration of genotoxic potential for α,β‐unsaturated alicyclic ketones and precursors from chemical subgroup 2.7 of FGE.19

Flavouring Group Evaluation 53 (FGE.53): Consideration of phenethyl alcohol, aldehyde, acid and related acetals and esters evaluated by JECFA (59th meeting) structurally related to phenethyl alcohol, aldehyde, esters and related phenylacetic acid esters e

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