Heritable translocations induced by dermal exposure of male mice to acrylamide

Adler, I.‐D.; Gonda, H.; Angelis, Martin Hrabé de; Jentsch, Isabell; Otten, Isa-Sybille; Speicher, Michael R.

doi:10.1159/000077501

Cited by 17 publications

(7 citation statements)

References 35 publications

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“…Favor and Shelby (2005) reviewed seven published studies that assessed the effectiveness of AA and GA in inducing transmitted reciprocal translocations or gene mutations in the mouse. Results indicated an increase in the frequency of translocation carriers in offspring following paternal exposure to AA or GA in spermatid and spermatozoa (Shelby et al, 1987;Adler, 1990;Adler et al, 1994Adler et al, , 2004Generoso et al, 1996). Even the dose of 50 mg AA/kg b.w.…”

Section: Genotoxicitymentioning

confidence: 99%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

341

170

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EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 µg/kg body weight (b.w.) per day and 0.6 to 3.4 µg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category 'Potato fried products (except potato crisps and snacks)'. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL 10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on acrylamide (AA) in food. The Panel developed the draft scientific opinion which underwent a public consultation from 1 July 2014 to 15 September 2014. The comments received and how they were taken into account when finalising the scientific opinion were published in an EFSA Technical Report (EFSA, 2015).AA is a low molecular weight, highly water soluble, organic compound. It is used inter alia as an industrial chemical and in the production of polyacrylamides. Heightened concerns about exposure to AA arose in 2002 when it was discovered that it forms when certain foods are prepared at temperatures usually above 120 °C and low moisture. It forms, at least in part, due to a Maillard reaction between certain amino acids, such as asparagine, and reducing sugars. However, several other pathways and precursors have also been proposed to contribute to AA formation. AA forms in numerous baked or fried carbohydrate-rich f...

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Section: Genotoxicitymentioning

confidence: 99%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

341

170

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“…Many compounds are capable of inducing DNA damage in the male germ line that then result in embryonic loss following insemination of untreated females including 1-bromopropane (widely used in spray adhesives, as a precision cleaner and a degreaser), acrylamide (present in fried food), radiation, chemotherapeutic agents, as well as metals such as iron and nickel, etc. (Adler et al, 2004;Doreswamy et al, 2004;Dobrzyń ska et al, 2005;Doreswamy & Muralidhara, 2005;Singer et al, 2006). Of particular interest, is the finding that streptozotocin, a diabetogen, can generate dominant lethal effects (Shrilatha & Muralidhara, 2007) in light of a recent data indicating that diabetic men possess high levels of oxidative DNA damage in their spermatozoa (Agbaje et al, 2008).…”

Section: The Biological and Clinical Significance Of Dna Damagementioning

confidence: 99%

Biological and clinical significance of DNA damage in the male germ line

Aitken¹,

Iuliis²,

2009

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DNA damage is a common feature of human spermatozoa with purported links to poor rates of conception, impaired embryonic development, an increased incidence of miscarriage and the appearance of various kinds of morbidity in the offspring including childhood cancer. However, difficulties in interpretation arise, because these associations are not consistently observed across all data sets. Such inconsistency reflects the inherent complexity of the reproductive process, large variations in sample size, differences in patient selection, inadequate study design as well as inter-individual differences in the type of DNA damage being detected and the effectiveness of repair mechanisms in the oocyte. This review considers the type, source and measurement of DNA damage in human spermatozoa. It also addresses the clinical utility of the information generated in such studies, and highlights areas where further research is needed to bridge the gap between an intriguing biological phenomenon and the evidence-based clinical management of male patients characterized by high levels of DNA damage in their spermatozoa.

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“…This pattern of sensitivity is in accord with several publications where maximal genetic damages have also been observed in early spermatids (Barnett and Lewis 2003;Codrington et al 2004). However, some chemicals, mainly alkylating agents, produce more dominant lethal mutations and translocations in late spermatids and early spermatozoa than in other germcell stages in male mice (Ehling 1980;Russell 2004;Adler et al 2004). In contrast, other chemicals, such as ethyl nitrosourea and methyl nitrosourea, show no germ cell stage-specific selection, with a wide range of effects on both pre-and postmeiotic cells (Sega et al 1981).…”

Section: Discussionmentioning

confidence: 99%

Mutagenicity of Ascaris chymotrypsin inhibitor in germ cells of mice

Błaszkowska

2007

Cell Biol Toxicol

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Chymotrypsin inhibitor isolated from Ascaris suum (ACHI) was tested for the induction of dominant lethal mutations in male mice. Dominant lethal effects of ACHI for the main stages of germ cell development were analyzed by mating at specific time points after dosing. Two groups of adult BALB/c males received 24 or 40 mg per kilogram body weight (BW) per day intraperitoneal (IP) injection of ACHI in sterile phosphate-buffered saline (PBS) for five consecutive days (subacute exposure). Males from a third group were administered single IP injections of ACHI-60 mg/kg BW (acute exposure). The control group received concurrent injections of PBS for five successive days. After the last dose, each male was mated with two untreated females. For fractionated examination with regard to successive germ cell stages (spermatozoa, spermatids, spermatocytes, spermatogonia), every second week, two other untreated virgin females were placed with each male for mating. The uteri of the females were inspected on the 15th day of gestation, and preimplantation loss and postimplantation loss determined from dominant lethal parameters. Exposure of mice germ cells to ACHI did not impair mating activity of males. Fertility index was reduced (P < 0.05) only for females mated at the third week with males exposed to the highest dose of ACHI. In the females bred to ACHI-treated males, significant (P < 0.05) increase in preimplantation loss was observed at postinjection weeks 1 (reflecting exposure to spermatozoa after single treatment and to spermatozoa or late spermatids after subacute dosing) and 3 (reflecting exposure to mid and early spermatids for acute dosing and to mid and early spermatids or late spermatocytes following acute treatment), regardless of dose and length of exposure to the inhibitor. At the 60-mg/kg-BW group, a significant increase of this parameter was also noted at week 5 (reflecting exposure to early spermatocytes). During mating days 15-21, a significant (P < 0.05) increase in postimplantation loss and dominant lethal effects were observed for all doses of ACHI. Acute ACHI exposure 5 weeks prior to mating resulted in dominant lethal effects in early spermatocytes. These preliminary data suggest that ACHI induces dominant lethal mutations at postmeiotic and meiotic stages of spermatogenesis, but spermatids are the most sensitive cell stage to the effect of ACHI. These results show that ACHI may be one of the factors causing disturbances in spermatogenesis leading to a reduction of host reproductive success.

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Heritable translocations induced by dermal exposure of male mice to acrylamide

Cited by 17 publications

References 35 publications

Scientific Opinion on acrylamide in food

Scientific Opinion on acrylamide in food

Biological and clinical significance of DNA damage in the male germ line

Mutagenicity of Ascaris chymotrypsin inhibitor in germ cells of mice

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