Local QSAR based on quantum chemistry calculations for the stability of nitrenium ions to reduce false positive outcomes from standard QSAR systems for the mutagenicity of primary aromatic amines.

Background: Primary aromatic amines (PAAs) present significant challenges in the prediction of mutagenicity using current standard quantitative structure activity relationship (QSAR) systems, which are knowledge-based and statistics-based, because of their low positive prediction values (PPVs). Previous studies have suggested that PAAs are metabolized into genotoxic nitrenium ions. Moreover, ddE, a relative-energy based index derived from quantum chemistry calculations that measures the stability nitrenium ions, has been correlated with mutagenicity.

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

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.

Evaluation of the novel liver micronucleus assay using formalin-fixed tissues.

Background: The repeated-dose liver micronucleus (RDLMN) assay is an effective and important in vivo test for detecting genotoxic compounds, particularly for those that require metabolic activation to show genotoxicity. In a collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/The Japanese Environmental Mutagen Society (JEMS) - Mammalian Mutagenicity Study Group (MMS), micronucleus induction of 22 chemicals with the RDLMN assay employing the collagenase digestion method was examined and reported on. Recently, we have developed a method which enables retrospective evaluation of micronucleus induction in formalin-fixed liver tissues (the formalin-fixed method) obtained in general toxicity studies completed in the past.

Pancreatic Ductal Adenocarcinoma in a Wistar Hannover GALAS Rat.

There are no reported spontaneous cases of pancreatic ductal adenocarcinoma (PDAC), and there are few reports about chemically-induced PDAC in rats. We encountered a PDAC in a Wistar Hannover GALAS rat that had been subjected to a medium-term multiorgan carcinogenicity bioassay. This article describes the histological and histochemical findings of the tumor.

Repeated dose liver micronucleus assay using adult mice with multiple genotoxicity assays concurrently performed as a combination test.

Recently, the liver micronucleus (MN) assay using young adult rats with repeated administrations has been investigated by employing a new method without partial hepatectomy or in situcollagenase perfusion as the repeated dose liver MN (RDLMN) assay by Narumi et al. (2012). In our study, in order to investigate the possibility of the RDLMN assay using young adult mice instead of rats and the feasibility of employing some genotoxicity assays along with the RDLMN assay as a combination test, two genotoxic carcinogens (N,N-diethylnitrosoamine (DEN) and cisplatin (CIS)) and a nongenotoxic carcinogen (phenobarbital sodium (PHE)) were administered to mice for 15 or 29 days.

Carcinogen-induced Thyroid Proliferative Lesions in Wistar Hannover GALAS Rats with Thyroid Dysplasia.

Incidences and morphological features of thyroid proliferative lesions induced by carcinogens in Wistar Hannover GALAS rats (GALAS rats) showing normal growth with or without thyroid dysplasia were examined. All thyroid tissue samples were obtained from our recently conducted study using male GALAS rats treated with 5 carcinogens according to the medium-term multiorgan carcinogenicity bioassay protocol (called DMBDD treatment). In the DMBDD-treated rats, thyroid dysplasia was found in 9 out of 114 rats.

Toxicological pathology in the rat placenta.

The placenta grows rapidly for a short period with high blood flow during pregnancy and has multifaceted functions, such as its barrier function, nutritional transport, drug metabolizing activity and endocrine action. Consequently, the placenta is a highly susceptible target organ for drug- or chemical-induced adverse effects, and many placenta-toxic agents have been reported. However, histopathological examination of the placenta is not generally performed, and the placental toxicity index is only the placental weight change in rat reproductive toxicity studies.

The use of an automated hematology analyzer to observe cell growth in the chromosome aberration test using human lymphocytes.

Human lymphocytes have been frequently used for in vitro chromosome aberration or micronucleus tests on whole-blood culture. However, it is difficult to observe or confirm the cell growth of lymphocytes just before chemical treatment compared with cultured cell lines, such as CHL or CHO cells. In order to overcome this drawback of using whole-blood culture, we investigated a possibility of using an automated hematology analyzer (AHA) (Sysmex XT-2000i, SYSMEX Corp.

Genotoxicity of 3,6-dinitrobenzo[e]pyrene, a novel mutagen in ambient air and surface soil, in mammalian cells in vitro and in vivo.

3,6-Dinitrobenzo[e]pyrene (3,6-DNBeP), newly identified in airborne particles and surface soil, is a potent mutagen in Salmonella typhimurium. The present study investigated the genotoxic potency of 3,6-DNBeP in vitro and in vivo using mammalian cell strains (Chinese hamster CHL/IU and human HepG2) and ICR mice, respectively. In the hprt gene mutation assay using HepG2 cells, the spontaneous mutant frequency was 61.