Dosage time affects alkylating agents induced micronuclei in mouse peripheral blood reticulocytes through the function of erythropoietin.

Previously, we reported that the frequency of micronucleated reticulocytes (MNRETs) in the peripheral blood of male C3H/He mice intraperitoneally administered ethylnitrosourea (ENU) (25 mg/kg body weight) in the dark period (zeitgeber time, ZT15) was higher than in the light period (ZT3). In this study, to clarify the mechanism underlying this phenomenon, we investigated the differences in micronucleus (MN) induction observed between ZT3 and ZT15 using five chemicals, methylnitrosourea (MNU), ethylmethane sulfonate (EMS), mitomycin C, cyclophosphamide and vincristin. MNU and EMS, monofunctional alkylating agents, showed higher frequencies of MNRETs in the ZT15 than the ZT3 treatment similar to ENU.

Chimeric mice with human hepatocytes: A new system for genotoxicity studies.

Genotoxicity assays are characterized by a method, an in vitro or in vivo target, and an endpoint. Many cell types have been used as targets, including bacterial cells, cultured mammalian cells, and rodent cells in vivo. Human cells are the most important target for evaluating the risk to humans associated with exposure to chemicals.

Anticarcinogenic Effects of Dried Citrus Peel in Colon Carcinogenesis Due to Inhibition of Oxidative Stress.

Colorectal cancer is one of the leading causes of death worldwide. Reactive oxygen species produce oxidative stress and contribute to colorectal carcinogenesis. Because dietary citrus has been shown to reduce oxidative stress, we investigated the effects of citrus peel extract at dilutions of 1/200-1/500 on the activity of oxidative-stress-related transcription factors, including AP-1, NF-κB, NRF2, p53, and STAT3, in human colon cancer cell line HCT116 cells using a luciferase reporter gene assay.

Reference control data obtained from an in vivo comet-micronucleus combination assay using Sprague Dawley rats.

According to the International Conference on Harmonization Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use (ICH S2(R1)), a positive response in any in vitro assay necessitates additional in vivo test(s) (other tissue/endpoint) in addition to the erythrocyte micronucleus test when Option 1 of the test battery is selected. When Option 2 of the test battery is selected, a bacterial gene mutation test and two in vivo tests with different tissues/endpoint are required. The in vivo alkaline comet assay is recommended as the second in vivo test because it can detect a broad spectrum of DNA damage in any tissue and can be combined with the erythrocyte micronucleus test.

Repeated-dose liver and gastrointestinal tract micronucleus assays for quinoline in rats.

Repeated-dose liver, bone marrow, and gastrointestinal tract micronucleus assays that use young adult rats were evaluated in a collaborative study that was organized by the Japanese Environmental Mutagen Society-Mammalian Mutagenicity Study Group. A genotoxic hepatocarcinogen quinoline was orally administered to independent groups of five Crl:CD (SD) male rats at doses of 30, 60 and 120mg/kg for 14 days and at doses of 15, 30 and 60mg/kg for 28 days. After treatment, the livers were harvested and hepatocytes were isolated by collagenase treatment.

Evaluation of in vivo mutagenicity of hydroquinone in Muta™ mice.

Hydroquinone (HQ) is used in skin bleaching agents, hair dyes, and finger nail treatments. Many skin-lightening cosmetics that contain HQ are currently marketed in Japan. Concerns have been expressed regarding health risks to the general population because the carcinogenicity of HQ was previously suggested in animal studies.

Flow cytometric analysis of micronuclei in rat peripheral blood: An interlaboratory reproducibility study.

In anticipation of proposed OECD guideline changes that may include increasing the number of reticulocytes scored for micronuclei, an inter-laboratory reproducibility study of the rat peripheral blood micronucleus assay was performed using flow cytometry. In this experiment, male Sprague-Dawley (SD) rats were treated with the model clastogen cyclophosphamide (CP: 5, 10 or 15mg/kg) by a single oral administration. As controls, rats were treated with physiological saline (solvent) in the same manner as for the model clastogen.

In vivo micronucleus assay in mouse bone marrow and peripheral blood.

The rodent micronucleus assay has been most widely and frequently used as a representative in vivo assay system to assess mutagenicity of chemicals, regardless of endpoint of mutagenicity. The micronucleus has been developed to assess induction of structural and numerical chromosomal aberrations of target chemical. In this chapter, we describe the standard protocols of the assay using mouse bone marrow and peripheral blood.

In vivo comet assay of multi-walled carbon nanotubes using lung cells of rats intratracheally instilled.

The genotoxicity of multi-walled carbon nanotubes (MWCNTs) was evaluated in vivo with comet assays using the lung cells of rats given MWCNTs. The MWCNTs were intratracheally instilled as a single dose at 0.2 or 1.

Differences in micronucleus induction in peripheral blood reticulocytes of mice exposed to N-ethyl-N-nitrosourea at light and dark dosing times.

Mammals, including human beings, have a circadian clock system to regulate behavioral and physiological processes. In this study, we investigated the effect of dosing time on micronucleus induction in the bone marrow by evaluating the frequencies of micronucleated peripheral reticulocytes (MNRETs) in mice exposed to N-ethyl-N-nitrosourea (ENU) to assess any difference in genotoxic sensitivity to chemicals between light and dark periods (inactive phase for rodents and active phase for rodents). Male C3H/He mice were treated intraperitoneally with ENU (12.

Studies of the toxicological potential of capsinoids: V. Genotoxicity studies of dihydrocapsiate.

A series of studies was performed to evaluate the safety of dihydrocapsiate (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS no. 205687-03-2). This study evaluated the potential genotoxicity of this compound using a variety of in vitro and in vivo test systems, including bacterial reverse mutation test, chromosomal aberration test, micronucleus test, gene mutation assay with transgenic rats, and single-cell gel (SCG) assay (Comet assay).

Studies of the toxicological potential of capsinoids: I. Single-dose toxicity study and genotoxicity studies of CH-19 Sweet extract.

A single-dose oral toxicity lethal-dose study was conducted to examine the toxicity of capsinoids contained in CH-19 Sweet extract. CH-19 Sweet extract was administered once by gavage to SPF (Crl:CD(SD)) Sprague-Dawley male and female rats at dose levels of 0 (vehicle), 5, 10, or 20 ml/kg of body weight (BW). The concentration of capsinoids in the CH-19 Sweet extract was 71.

Formation of mutagenic/carcinogenic heterocyclic amines under moderate conditions.

More than 10 kinds of heterocyclic amines (HCAs), showing mutagenic and carcinogenic potency, have been isolated from cooked fish and meat. But many researchers say that the contribution ratio of HCAs to human cancer is very low. Our purpose in this experiment was to investigate the possibility of the formation of HCAs under moderate conditions, including in vivo.