Effect of sampling time on somatic and germ cell mutations induced by acrylamide in gpt delta mice

Abstract

Background Acrylamide (AA) is a rodent carcinogen and classified by the IARC into Group 2A (probable human carcinogen). AA has been reported to induce mutations in transgenic rodent gene mutation assays (TGR assays), the extent of which is presumed to depend on exposure length and the duration of expression after exposure. In particular, it is not clear in germ cells. To investigate mutagenicity with AA in somatic and germ cells at different sampling times, we conducted TGR assays using gpt delta transgenic mice. Results The male gpt delta mice at 8 weeks of age were treated with AA at 7.5, 15 and 30 mg/kg/day by gavage for 28 days. Peripheral blood was sampled on the last day of the treatment for micronucleus tests and tissues were sampled for gene mutation assays at day 31 and day 77, those being 3 and 49 days after the final treatment (28 + 3d and 28 + 49d), respectively. Another group of mice was treated with N-Ethyl-N-nitrosourea (ENU) at 50 mg/kg/day by intraperitoneal administration for 5 consecutive days and tissues were sampled at the day 31 and day 77 (5 + 26d and 5 + 72d). Frequencies of micronucleated erythrocytes in the peripheral blood significantly increased at AA doses of 15 and 30 mg/kg/day. Two- to three-fold increases in gpt mutation frequencies (MFs) compared to vehicle control were observed in the testes and lung treated with 30 mg/kg/day of AA at both sampling time. In the sperm, the gpt MFs and G:C to T:A transversions were significantly increased at 28 + 3d, but not at 28 + 49d. ENU induced gpt mutations in these tissues were examined at both 5 + 26d and 5 + 72d. A higher mutant frequency in the ENU-treated sperm was observed at 5 + 72d than that at 5 + 26d. Conclusions The gpt MFs in the testes, sperm and lung of the AA-treated mice were determined and compared between different sampling times (3 days or 49 days following 28 day-treatment). These results suggest that spermatogonial stem cells are less sensitive to AA mutagenicity under the experimental condition. Prolonged expression time after exposure to AA to detect mutagenicity may be effective in somatic cells but not in germ cells.

Estimation of genotoxicity, apoptosis and oxidative stress induction by TiO2 nanoparticles and acrylamide subacute oral coadministration in mice

“…According to the results of the comet assay, the current study found that multiple oral administrations of either acrylamide (3 mg/kg b.w) or TiO 2 NPs (5 mg/kg b.w) exposure dose caused high DNA breakages as manifested by the remarkable statistically significant increase observed in comet parameters: tail length, %DNA in tail and tail moment compared to negative control values. These results confirmed the DNA damage induction by acrylamide 13 , 15 – 18 or TiO 2 NPs 2 , 3 , 6 , 8 , 9 reported in previous studies. Moreover, oral simultaneous coadministration of acrylamide with TiO 2 NPs augmented genomic DNA disruption and damage as indicated by the observed remarkable elevations in tail length, %DNA in tail and tail moment compared to their values in mice orally given TiO 2 NPs alone.…”

“…Acrylamide can be found in fried, baked and grilled dishes in the highest concentrations 12 . Clastogenicity and genotoxicity of acrylamide have been demonstrated in different experimental systems as manifested by the induction of chromosomal aberrations, DNA damage and mutations observed in mice and rats after administration of acrylamide 13 – 18 .…”

Assessment of the genotoxicity of acrylamide

“…Mutational spectra were similar for the two compounds that mainly affected GC > TA, AT > TA and AT > CG mutations (Li et al, 2016 ). Increased mutation frequencies were also reported at the gpt gene in the testis, lung (two‐ to threefold increase) and sperm (sixfold increase) of C57BL/6J mice treated with AA (Hagio et al, 2021 ). The mutational classes involved varied between organs: GC > TA, GC > AT and 1‐bp deletions predominated in sperm, whereas AT > TA mutations were the major class involved in the lung.…”

“…In three strains of mice (B6C3F1, Swiss albino, C57BL/6J), in vivo oral exposure to AA was consistently positive in micronucleus tests in the bone marrow or peripheral blood (Hobbs et al, 2016;Algarni, 2018;Hagio et al, 2021) (see Table 2). In more limited studies, a single i.p.…”

Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk

“…In rats dosed with AC at 2 or 15 mg/kg bw for up to 28 days, DNA synthesis was increased in target tissues, but not in a non-target tissue, the liver [ 411 ]. In mice, administration of AC at 7.5, 15 and 30 mg/kg bw/day by gavage for 28 days produced a significant increase in micronuclei formation in the peripheral blood and an increase in gpt mutation frequencies in testes and lungs [ 412 ]. In addition, AC induced DNA strand breaks in various tissues in rats and mice [ 413 , 414 , 415 ].…”