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PubMed2005

Determination of DNA base composition by small scale acrylamide-CsCl gradient centrifugation.

In this paper we describe a simple and rapid protocol for DNA base composition determination by CsCl gradient in the presence of acrylamide. This method permits the determination of GC content in microgram amounts of DNA, and results are easily documented in photographs or graphs. The protocol was applied to the characterization of nematode DNA, but can be used for other organisms. Analyzing several experiments the mean standard deviation observed in the calculated GC content is near 1.3%.

Acrylamide↗
PubMed2005

Targeting normal and neoplastic tissues in the rat jejunum and colon with boronated, cationic acrylamide copolymers.

A series of boronated cationic copolymers, composed of different ratios of acrylamide, N-acryloyl-3-aminophenylboronic acid and N-acryloyl-diaminoethane (the cationic moiety), were prepared with the intention of localizing boron neutron capture therapy (BNCT) in experimentally induced polyps on the luminal side of the gut of the rat. The goals of this study were to: (a) test the effect of cationization of the boronated copolymers on their uptake by polyps and normal adjacent epithelium; (b) compare the whole rat body distribution of aminophenylboronic acid (APB) and polymeric APB after local application; (c) measure the effect of micro-environmental parameters such as pH, the presence of mucin and cations on the interaction between the APB-copolymers and the epithelium of the rat intestines. Direct analysis of tissue boron levels showed that polymeric APB-uptake was higher in the colonic polyps than in the surrounding normal tissues. Free APB, however, was found in similar quantities in both. When tested in the normal jejunum and colon of the rat, polymeric APB uptake was directly proportional to the molar content of the cationic monomer in the copolymers. The presence of magnesium ions, free boron cationic monomer and mucin interfered with this uptake in a concentration-dependent manner. The uptake was pH-independent at pH 5, 7 and 10. APB accumulation in the colon polyps was inversely proportional to the cationic monomer content in the copolymers, suggesting an increased amount of mucus around the polyps, which probably impeded the electrostatic attachment of the polymer to the malignant tissue. The use polymeric APB for targeting BNCT in perioperative treatment of colorectal carcinoma is suggested, especially in the cases of microscopic residual disease after curative resection.

1,2-Dimethylhydrazine↗
PubMed2005

A comparison of genotoxicity between three common heterocyclic amines and acrylamide.

Heterocyclic amines (HCAs), a group of genotoxic compounds formed during the heating of proteinaceous food items, have been known since the late 1970s. However, the genotoxic effect of these compounds in the low dose region has not yet been thoroughly studied. Here we used a sensitive flow cytometer-based micronucleus assay in mice to determine the frequency of micronucleated erythrocytes (fMPCE) of the three common HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), in the low dose region. We especially looked for any deviation from linearity of the dose-response curves. Male Balb/C mice were intra peritoneally injected with different doses of either PhIP (0-36 mg/kg b.w.), MeIQx (0-90 mg/kg b.w.) or IQ (0-40 mg/kg b.w.). In the case of PhIP, we found a significant dose-response relationship, while MeIQx and IQ did not display an increased fMPCE level. This flow cytometer method allows for determination of the DNA content of micronuclei. All three HCAs tested here yielded a low DNA content of micronuclei, indicating that they do not possess aneugenic effects. A comparison between the HCAs and acrylamide (AA), another heat induced genotoxic compound, revealed that the slope of the dose-response curve is about 10 times steeper for PhIP than AA. In spite of this, AA probably constitutes a higher human risk than HCAs since the intake is about a 100- to 1000-fold higher than the intake of HCAs.

Acrylamide↗
PubMed2005

DNA adducts derived from administration of acrylamide and glycidamide to mice and rats.

Acrylamide (AA) is an important industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in chronic rodent bioassays. Recent findings of AA in many common starchy foods have sparked renewed interest in determining toxic mechanisms and in understanding the cancer, neurotoxicity, and reproductive risks from typical human exposures. Dosing mice and rats with AA (50 mg/kg) led to presence of glycidamide (GA) in serum and tissues. Furthermore, GA-derived DNA adducts of adenine and guanine were formed in all tissues examined, including both target tissues identified in rodent carcinogenicity bioassays and in non-target tissues. Dosing rats and mice with an equimolar amount of GA typically produced higher levels of DNA adducts than observed with AA. Kinetics of DNA adduct formation and accumulation were measured following oral administration of a single dose of AA (50 mg/kg) or from repeat dosing (1 mg/kg/day), respectively. The formation of these DNA adducts is consistent with previously reported mutagenicity of AA and GA in vitro, which involved reaction of GA with adenine and guanine bases. These results provide strong support for a genotoxic mechanism of AA carcinogenicity in rodents. The kinetic/biomarker approaches described here may represent a meaningful way to extrapolate cancer risks to actual human exposures from food, which are much lower.

Acrylamide↗
PubMed2005

Calculations of dietary exposure to acrylamide.

In this paper we calculated the usual and acute exposure to acrylamide (AA) in the Dutch population and young children (1-6 years). For this AA levels of different food groups were used as collected by the Institute for Reference Materials and Measurements (IRMM) of the European Commission's Directorate General Joint Research Centre (JRC) from April 2003 up to May 2004. This database contained about 3500 AA levels received from mainly Germany, The Netherlands, Ireland, Greece, Austria, UK and from food industry. Food consumption levels used were derived from the Dutch National Food Consumption Survey of 1997/1998 (n=6250 of which 530 children aged 1-6 years). The exposure was estimated using the probabilistic approach. The results of the exposure calculations are discussed in relation to different methodological aspects of AA exposure calculations and possible uncertainties related to this. The items discussed include quality of the AA levels measured in food items, the allocation of AA levels to food categories, the quality of food consumption levels, and relevant exposure model in relation to reported toxicity of AA. Furthermore, we demonstrate that scenario studies and probabilistic modelling of exposure are potential useful tools to evaluate the effect of processing techniques to reduce AA levels in food on AA exposure. The scenarios studied reduced total AA exposure ranging from <1% up to 17%.

Acrylamide↗
PubMed2005

Acrylamide and glycidamide: genotoxic effects in V79-cells and human blood.

Acrylamide (AA) can be formed in certain foods by heating, predominantly from the precursor asparagine. It is a carcinogen in animal experiments, but the relevance of dietary exposure for humans is still under debate. There is substantial evidence that glycidamide (GA), metabolically formed from AA by Cyp 2E1-mediated epoxidation, acts as ultimate mutagenic agent. We compared the mutagenic potential of AA and GA in V79-cells, using the hprt mutagenicity-test with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) as positive control. Whereas MNNG showed marked mutagenic effectivity already at 0.5 microM, AA was inactive up to a concentration of 10 mM. In contrast, GA showed a concentration dependent induction of mutations at concentrations of 800 microM and higher. Human blood was used as model system to investigate genotoxic potential in lymphocytes by single cell gel electrophoresis (comet assay) and by measuring the induction of micronuclei (MN) with bleomycin (BL) as positive control. AA did not induce significant genotoxicity or mutagenicity up to 6000 microM. With GA, concentration dependent DNA damage was observed in the dose range of 300-3000 microM after 4 h incubation. Significant MN-induction was not observed with AA (up to 5000 microM) and GA (up to 1000 microM), whereas BL (4 microM) induced significantly enhanced MN frequencies. Thus, in our systems GA appears to exert a rather moderate genotoxic activity.

Acrylamide↗
PubMed2005

Differences in hemoglobin adduct levels of acrylamide in the general population with respect to dietary intake, smoking habits and gender.

The variation in dietary exposure to acrylamide (AA) has been studied through measurement of hemoglobin adduct levels from AA, as a measurement of internal dose, in a sample from the blood bank of the Malmö Diet and Cancer Cohort (n=28,098). The blood donors are well characterised with regard to their food habits, and 142 individuals were selected to obtain highest possible variation in the adduct levels from AA (none, random or high intake of coffee, fried potato, crisp bread and snacks, food items estimated to have high levels of AA). Among 70 non-smokers the AA-adduct levels varied by a factor of 5, and ranged between 0.02 and 0.1 nmol/g, with considerable overlap in AA-adduct levels between the different dietary groups. There was a significant difference between men with high dietary exposure to AA compared to men with low dietary exposure (P=0.04). No such difference was found for women. As expected a higher level (range: 0.03-0.43 nmol/g) of the AA-adduct, due to AA in tobacco smoke, was found in smokers. Smoking women with high dietary exposure to AA had significantly higher AA-adduct levels compared to smoking women with low dietary exposure (P=0.01). No such significant difference was found in smoking men. The median hemoglobin (Hb) adduct level in the randomly selected group of non-smokers was compatible with earlier studies (0.031 nmol/g). The variation in the average internal dose, measured as Hb adducts, was somewhat smaller than estimated for daily intake by food consumption questionnaires in other studies. Thus, the observed relatively narrow inter-individual variation in AA-adduct levels means that estimates of individual dietary AA intake have to be very precise if they should be useful in future cancer epidemiology.

Acrylamide↗
PubMed2005

DNA strand breaking capacity of acrylamide and glycidamide in mammalian cells.

We compared the DNA damaging potency of acrylamide (AA) and its metabolite glycidamide (GA) in the comet assay in cell systems differing with respect to species origin and cytochrome P450-depended monooxygenase (CYP2E1) expression (V79, Caco-2, primary rat hepatocytes). Only after 24 h incubation in the highest concentration of AA (6 mM) a slight but significant increase in DNA damage was observed in V79 and Caco-2 cells. In primary rat hepatocytes, however, expressing substantial amounts of CYP2E1, no induction of DNA strand breaks was found. At the end of the incubation time period (24 h), still 67+/-19% of the CYP2E1 protein was detected by Western blotting. Direct treatment with GA resulted in a significant increase in DNA damage in V79 cells and primary rat hepatocytes at concentrations > or =100 microM (24 h). Caco-2 cells were found to be less sensitive, exhibiting an increase in DNA strand breaks at concentrations > or 300 microM GA. These data confirm the higher genotoxic potential of GA compared to AA but also indicate that high expression of CYP2E1 per se is not necessarily associated with increased genotoxicity of AA. We, therefore, investigated whether the intracellular glutathione (GSH) level might be a critical determinant for the genotoxicity of AA in cells with different CYP2E1 status. Depletion of intracellular GSH by dl-buthionine-[S,R]-sulfoxime (BSO) in rat hepatocytes and V79 cells resulted in a significant induction of DNA strand breaks after incubation with 1 mM AA. However, at higher concentrations (> or =1.25 mM) a strong increase in cytotoxicity, resulting in a severe loss of viability, was observed. In summary, the DNA strand breaking effect of AA appeared not to be directly correlated with the CYP2E1 status of the cells. Depletion of GSH is associated with an increase in AA genotoxicity but seems also to lead to a substantial enhancement of cytotoxicity.

Acrylamide↗
PubMed2006

Genotoxicity of acrylamide and glycidamide in human lymphoblastoid TK6 cells.

The recent finding that acrylamide (AA), a potent carcinogen, is formed in foods during cooking raises human health concerns. In the present study, we investigated the genotoxicity of AA and its metabolite glycidamide (GA) in human lymphoblastoid TK6 cells examining three endpoints: DNA damage (comet assay), clastogenesis (micronucleus test) and gene mutation (thymidine kinase (TK) assay). In a 4 h treatment without metabolic activation, AA was mildly genotoxic in the micronucleus and TK assays at high concentrations (> 10 mM), whereas GA was significantly and concentration-dependently genotoxic at all endpoints at > or = 0.5 mM. Molecular analysis of the TK mutants revealed that AA predominantly induced loss of heterozygosity (LOH) mutation like spontaneous one while GA-induced primarily point mutations. These results indicate that the genotoxic characteristics of AA and GA were distinctly different: AA was clastogenic and GA was mutagenic. The cytotoxicity and genotoxicity of AA were not enhanced by metabolic activation (rat liver S9), implying that the rat liver S9 did not activate AA. We discuss the in vitro and in vivo genotoxicity of AA and GA.

Acrylamide↗
PubMed2006

Anti-genotoxic effect of Aloysia triphylla infusion against acrylamide-induced DNA damage as shown by the comet assay technique.

Aloysia triphylla a perennial, bushy plant originally from South America has long been used in traditional medicine. Its aqueous extract contains considerable amounts of polyphenolic compounds, namely flavonoids and phenolic acids. In view of the interest in natural phenolic compounds as antioxidant in preventive medicine, this study was undertaken to investigate the chemoprotective effects of cedron leaves infusion against the genetic damage induced by acrylamide (AA) by using the alkaline version of the comet assay technique. Mice were separated in nine groups (eight animals each): (I) untreated, (II) negative control, (III) treated with infusion of cedron leaves 5%, 20 days twice a day, (IV) treated with AA (5 mg/kg b.w.), (V) treated with AA (20 mg/kg b.w.), (VI) treated with AA (30 mg/kg b.w.), (VII) treated with AA (50 mg/kg b.w.), (VIII) pretreated with infusion and treated with AA (50 mg/kg b.w.) and (IX) positive control (cyclophosphamide, 20 mg/kg b.w.). Three hundred blast cells were digitally evaluated per animal from three different slides (100 each). Media of tail moment (TM) values were analyzed by ANOVA test. No statistical differences (p>0.05) were found between untreated animals, negative control and infusion-treated mice. A single dose of AA-induced genetic damage as revealed by a statistically significant increase in TM values (p<0.01). Pretreatment with infusion prior to AA injection significantly reduces the capacity of AA to induce genetic damage. In these conditions, tail moments values did not differ from data obtained in negative control (p>0.05) and exhibit statistical differences from animals treated only with AA (p<0.01). Cell viability was at least 90% in all cases as measured by the trypan blue exclusion method. The ferric reducing ability of plasma (FRAP) method reveals that the plasma of infusion-treated mice has a significantly higher antioxidant capacity than plasma from controls (p<0.01). The results suggest that the infusion could exerts an in vivo chemo protective action, probably due to its scavenging potency towards free radicals.

Acrylamide↗
PubMed2004

The changing view of acrylamide neurotoxicity.

Acrylamide (ACR) is a water-soluble, vinyl monomer that has multiple chemical and industrial applications: e.g., waste water management, ore processing. In addition, ACR is used extensively in molecular laboratories for gel chromatography and is present in certain foods that have been prepared at very high temperatures. Extensive studies in rodents and other laboratory animals have provided evidence that exposure to monomeric ACR causes cellular damage in both the nervous and reproductive systems, and produces tumors in certain hormonally responsive tissues. Whereas human epidemiological studies have demonstrated a significantly elevated incidence of neurotoxicity in occupationally exposed populations, such research has not, to date, revealed a corresponding increase in cancer risk. Since the announcement by a Swedish research group in April 2002 [J. Ag. Food Chem. 50 (2002) 4998] regarding the presence of ACR in potato and grain-based foods, there has been a renewed interest in the toxic actions of this chemical. Therefore, in this review, we consider the different toxic effects of ACR. The neurotoxic actions of ACR will be the focal point since neurotoxicity is a consequence of both human and laboratory animal exposure and since this area of investigation has received considerable attention over the past 30 years. As will be discussed, a growing body of evidence now indicates that the nerve terminal is a primary site of ACR action and that inhibition of corresponding membrane-fusion processes impairs neurotransmitter release and promotes eventual degeneration. The electrophilic nature of ACR suggests that this neurotoxicant adducts nucleophilic sulfhydryl groups on certain proteins that are critically involved in membrane fusion. Adduction of thiol groups also might be common to the reproductive and carcinogenic effects of ACR. A final goal of this review is to identify data gaps that retard a comprehensive understanding of ACR pathophysiological processes.

Acrylamide↗
PubMed2006

The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.

The family of Kv7 (KCNQ) potassium channels consists of five members. Kv7.2 and 3 are the primary molecular correlates of the M-current, but also Kv7.4 and Kv7.5 display M-current characteristics. M-channel modulators include blockers (e.g., linopirdine) for cognition enhancement and openers (e.g., retigabine) for treatment of epilepsy and neuropathic pain. We investigated the effect of a Bristol-Myers Squibb compound (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide [(S)-1] on cloned human Kv7.1-5 potassium channels expressed in Xenopus laevis oocytes. Using two-electrode voltage-clamp recordings we found that (S)-1 blocks Kv7.1 and Kv7.1/KCNE1 currents. In contrast, (S)-1 produced a hyperpolarizing shift of the activation curve for Kv7.2, Kv7.2/Kv7.3, Kv7.4 and Kv7.5. Further, the compound enhanced the maximal current amplitude at all potentials for Kv7.4 and Kv7.5 whereas the combined activation/block of Kv7.2 and Kv7.2/3 was strongly voltage-dependent. The tryptophan residue 242 in S5, known to be crucial for the effect of retigabine, was also shown to be critical for the enhancing effect of (S)-1 and BMS204352. Furthermore, no additive effect on Kv7.4 current amplitude was observed when both retigabine and (S)-1 or BMS204352 were applied simultaneously. In conclusion, (S)-1 differentially affects the Kv7 channel subtypes and is dependent on a single tryptophan for the current enhancing effect in Kv7.4.

Acrylamides↗
PubMed2005

Developmental and behavioral effects of acrylamide in Fischer 344 rats.

Human exposures to acrylamide (ACR), a known neurotoxicant, can occur via a variety of substances, including cigarette smoke and the ingestion of certain carbohydrate-based foods cooked at high temperatures. In this study, Fischer 344 sperm plug-positive female rats were treated daily with ACR (0, 0.5, 1.0, 2.5, 5.0 or 10.0 mg/kg/day) by gavage beginning on gestation day 7. Dosing of dams ended when litters were born; pups received daily gavage at the same dose as their dam from postnatal day (PND) 1 through PND22. Pups were tested using a battery of behavioral assessments from PNDs 4-22. Statistically significant decreases in body weight were observed in pups exposed to ACR at doses as low as 1.0 mg/kg/day (treatmentxday; repeated measures ANOVA, P<0.0001). No statistically significant differences among treatment groups were observed in righting reflex, forelimb hang, or open field measures of activity. Statistically significant effects of ACR were observed at the 10 mg/kg/day dose on negative geotaxis performance (P<0.01) and a linear trend in fall-time latencies on Rotarod performance on PNDs 21-22 (P<0.05), with higher doses producing shorter latencies. These results suggest that ACR exposure produces deficits in development and motor coordination that are observable before weaning.

Acrylamide↗
PubMed2004

Proteomic analysis of acrylamide-protein adduct formation in rat brain synaptosomes.

Evidence suggests that the neurological defects (gait abnormalities, foot splay, and skeletal muscle weakness) associated with acrylamide (ACR) intoxication are mediated by impaired neurotransmission at central and peripheral synapses. ACR can form adducts with nucleophilic residues on proteins and thereby alter corresponding structure and function. To evaluate protein adduction in nerve terminals as a possible mechanism of action, recombinant N-ethylmaleimide sensitive factor (NSF) was exposed in vitro to ACR (10 micromol) and mass spectrometry (MS) was used to identify adduct sites. MS analyses demonstrated that ACR formed adducts with sulfhydryl groups on cysteine residues (carbamoylethylcysteine, or CEC) of NSF. Ex vivo incubation of whole brain synaptosomes with ACR (0.001-1.0 M) produced concentration-dependent increases in CEC that were inversely correlated to reductions in neurotransmitter release that occurred over the same neurotoxicant concentration range. In synaptosomes isolated from rats intoxicated at a higher (50 mg/kg per day x 3, 5, 8, or 11 days) or a lower (21 mg/kg per day x 14, 21, or 28 day) ACR dose rate, CEC levels increased progressively up to a moderate level of neurotoxicity. To identify protein adducts, synaptosomal proteins labeled by ex vivo 14C-ACR exposure were separated by gel electrophoresis and probed by immunoblot analysis. Results showed that NSF and the SNARE protein, SNAP-25, were tentative ACR targets. Subsequent experiments indicated that ACR exposure increased synaptosomal levels of the 7S SNARE core complex, which is consistent with inhibition of NSF, SNAP-25 function, or both. These data suggest that adduction of cysteine residues on NSF and certain SNARE proteins might be causally involved in the nerve terminal dysfunction induced by ACR.

Acrylamides↗
PubMed2005

Toxicokinetics of acrylamide and glycidamide in B6C3F1 mice.

Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxic mechanisms, particularly toxicokinetics and bioavailability. This study compares the toxicokinetics of AA and its epoxide metabolite glycidamide (GA) in serum and tissues of male and female B6C3F1 mice following acute dosing by intravenous, gavage, and dietary routes at 0.1 mg/kg AA or intravenous and gavage dosing with an equimolar amount of GA. AA was rapidly absorbed from oral dosing, was widely distributed to tissues, was efficiently converted to GA, and increased levels of GA-DNA adducts were observed in liver after complete elimination from serum. GA dosing also resulted in rapid absorption, wide distribution to tissues, and produced liver DNA adduct levels that were approximately 40% higher than those from an equimolar dose of AA. While oral administration was found to attenuate AA bioavailability to 23% from the diet and to 32-52% from aqueous gavage, a first-pass effect or other kinetic change resulted in higher relative internal exposure to GA when compared to the intravenous route. A similar effect on relative GA exposure was also evident as the administered dose was reduced, which suggests that as dosing rate decreases, the conversion of AA to GA is more efficient. These findings are critical to the assessment of genotoxicity of AA at low doses in the food supply, which appears to depend on total exposure to GA.

Acrylamide↗
PubMed2005

Toxicokinetics of acrylamide and glycidamide in Fischer 344 rats.

Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxic mechanisms, particularly toxicokinetics and bioavailability. This study compares the toxicokinetics of AA and its epoxide metabolite, glycidamide (GA), in serum and tissues of male and female F344 rats following acute exposure by intravenous, gavage, and dietary routes at 0.1 mg/kg AA or intravenous and gavage routes with an equimolar amount of GA. AA was rapidly absorbed after oral dosing, was widely distributed to tissues, was efficiently converted to GA, and produced increased levels of GA-DNA adducts in liver. GA was also rapidly absorbed, widely distributed to tissues, and produced increased liver DNA adduct levels. AA bioavailability after aqueous gavage was 60--98% and from the diet was 32--44%; however, first-pass metabolism or other kinetic change resulted in much higher internal exposures to GA (2- to 7-fold) when compared to the intravenous route. A similar effect on metabolism to GA following oral administration was previously observed under an identical exposure paradigm in mice. Furthermore, DNA adduct formation in rat liver showed the same proportionality with the respective GA AUC value as did mice in the previous study. These findings suggest that as the AA content in food is reduced, species-differences in GA formation and subsequent DNA adduct formation may be minimized. These findings provide additional information needed to assess genotoxic risks from the low levels of AA that are pervasive in the food supply.

Acrylamide↗
PubMed2005

Effect of subchronic exposure to acrylamide induced on the expression of bcl-2, bax and caspase-3 in the rat nervous system.

Occupational exposure and experimental intoxication with acrylamide (ACR) produce a neuropathy characterized by nerve degeneration. We hypothesize that ACR differentially affects the expression of bcl-2, bax and caspase-3 in the central nervous system (CNS) and the peripheral nervous system (PNS) tissue. Male adult Wistar rats were given ACR (20, 40 mg/kg i.p. 3 days/week) for 8 weeks. Samples of the cerebral cortex, cerebellum, spinal cord and sciatic nerves were collected and examined for bcl-2, bax and caspase-3 expression using Western blotting. Subchronic exposure to ACR reduced cortical bcl-2 expression in the low dose, increased it in the high dose; the change of bcl-2 expression in the spinal cord and cerebellum followed the same pattern as that described in the cerebral cortex; there was no significant change in the expression of bax in the cerebral cortex and the spinal cord, however, in the cerebellum the change of bax expression and bcl-2 expression is just the reverse. Thus, the bcl-2/bax ratio of the CNS tissue was affected by exposure to ACR, it decreased in the low dose group and increased in the high group. Compared to control, densitometric analysis showed that in the sciatic nerves the expression of bcl-2 and bax expression was markedly increased following ACR administration. The expression of inactive isoforms (32 kDa) of caspase-3 was not altered in the cortices of ACR-treated rats, but increased in their spinal cords and sciatic nerves. Thus, subchronic exposure to ACR affected the expression of death-related proteins in the CNS and PNS tissue, which indicate there is the early molecular regulatory mechanism of apoptosis in the neuropathy induced by ACR.

Acrylamide↗
PubMed2005

Adduction of biomacromolecules with acrylamide (AA) in mice at environmental dose levels studied by accelerator mass spectrometry.

Since 2002, WHO has strongly called scientists to investigate intensively the toxicity and potential carcinogenicity of acrylamide (AA), because humans are widely exposed to AA via various foodstuffs. In this study we measured the biomacromolecule adducts of [2,3-(14)C]AA (0, 7.5 x 10(-2), 7.5 x 10(-1), 7.5, 9.3 x 10(1), 2.4 x 10(2) and 1.0 x 10(3)microg/kg b.w.) in adult male mice by ultrasensitive accelerator mass spectrometry (AMS) technique. The aim is to evaluate the potential molecular toxicity of AA at human relevant dose levels, particularly towards the sperm cells. Hemoglobin (Hb), serum albumin (SA), protamine, sperm DNA, tails and heads were isolated 24h post dosing and the adduct levels were measured by AMS, respectively. Good log/log linear dose-response correlations were established. Moreover, the correlation of AA-protamine adducts, AA-sperm DNA adducts, as well as AA-sperm head/tail adducts with AA-Hb or AA-SA adducts presented a linear log/log mode. In sperm, the formation of AA-protamine adducts were predominating to AA-DNA adducts. The adducts on sperm heads/tails might both influence the fertility efficacy.

Acrylamide↗