Tumorigenicity of cyclopenta[α]phenanthrene derivatives and micronucleus induction in mouse skin

Baker, R.S.U.; Bonin, Antonio M.; Arlauskas, Andrew; He, Shuilin; Coombs, Maurice M.

doi:10.1093/carcin/13.3.329

Cited by 10 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The skin is the site of exposure to many chemicals in the environment, including industrial chemicals, pesticides, cosmetics, and external medicines that are applied to the skin surface. The skin micronucleus test has been developed as an in vivo/in vitro assay with mice Baker, 1989, 1991;Baker et al, 1992;Haesen et al, 1993]. Recently, a skin micronucleus assay with rats has also been developed [Nishikawa et al, 2000].…”

Section: Skinmentioning

confidence: 99%

In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring

Hayashi¹,

MacGregor²,

Gatehouse³

et al. 2000

Environ. Mol. Mutagen.

236

107

View full text Add to dashboard Cite

An expert working group on the in vivo micronucleus assay, formed as part of the International Workshop on Genotoxicity Test Procedures (IWGTP), discussed protocols for the conduct of established and proposed micronucleus assays at a meeting held March 25–26, 1999 in Washington, DC, in conjunction with the annual meeting of the Environmental Mutagen Society. The working group reached consensus on a number issues, including: (1) protocols using repeated dosing in mice and rats; (2) integration of the (rodent erythrocyte) micronucleus assay into general toxicology studies; (3) the possible omission of concurrently‐treated positive control animals from the assay; (4) automation of micronucleus scoring by flow cytometry or image analysis; (5) criteria for regulatory acceptance; (6) detection of aneuploidy induction in the micronucleus assay; and (7) micronucleus assays in tissues (germ cells, other organs, neonatal tissue) other than bone marrow. This report summarizes the discussions and recommendations of this working group. In the classic rodent erythrocyte assay, treatment schedules using repeated dosing of mice or rats, and integration of assays using such schedules into short‐term toxicology studies, were considered acceptable as long as certain study criteria were met. When the micronucleus assay is integrated into ongoing toxicology studies, relatively short‐term repeated‐dose studies should be used preferentially because there is not yet sufficient data to demonstrate that conservative dose selection in longer term studies (longer than 1 month) does not reduce the sensitivity of the assay. Additional validation data are needed to resolve this point. In studies with mice, either bone marrow or blood was considered acceptable as the tissue for assessing micronucleus induction, provided that the absence of spleen function has been verified in the animal strains used. In studies with rats, the principal endpoint should be the frequency of micronucleated immature erythrocytes in bone marrow, although scoring of peripheral blood samples gives important supplementary data about the time course of micronucleus induction. When dose concentration and stability are verified appropriately, concurrent treatment with a positive control agent is not necessary. Control of staining and scoring procedures can be obtained by including appropriate reference samples that have been obtained from a separate experiment. For studies in rats or mice, treatment/sampling regimens should include treatment at intervals of no more than 24 hr (unless the test article has a half‐life of more than 24 hr) with sampling of bone marrow or blood, respectively, within 24 or 40 hr after the last treatment. The use of a DNA specific stain is recommended for the identification of micronuclei, especially for studies in the rat. In the case of a negative assay result with a non‐toxic test article, it is desirable that systemic exposure to the test article is demonstrated. The group concluded that successful application of automated scoring by...

show abstract

Section: Skinmentioning

confidence: 99%

In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring

Hayashi¹,

MacGregor²,

Gatehouse³

et al. 2000

Environ. Mol. Mutagen.

236

107

View full text Add to dashboard Cite

show abstract

“…The assay for micronucleus induction in skin keratinocytes was performed as described by Baker et al [1992], with minor modifications. On the day prior to sacrifice, mouse skin was treated with hair remover (Nair, Carter-WallacePty.…”

Section: Micronuclei In Skin Keratinocytesmentioning

confidence: 99%

Determination of genotoxic and other effects in mice following short term repeated‐dose and subchronic inhalation exposure to phosphine

Barbosa¹,

Rosinova²,

Dempsey

et al. 1994

Environ and Mol Mutagen

View full text Add to dashboard Cite

Phosphine is an important fumigant in the grain industry and has been reported to be genotoxic in occupationally exposed fumigators. This study reports on the effects of phosphine inhalation exposure at up to, and exceeding, occupational relevant levels in a subchronic (0.3, 1.0 and 4.5 ppm, 13 weeks) and a short term repeated-dose (5.5 ppm, 2 weeks) study in both sexes of Balb-c mice. The following end-points were examined: micronucleus induction in bone marrow, peripheral blood, spleen lymphocytes and skin keratinocytes, mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in lymphocytes, and weight gain and relative organ weights (kidneys, lungs, liver, heart, brain and spleen). After subchronic exposure, there was a highly significant negative linear correlation between proportional weight gain and exposure in both sexes (multiple linear regression, r = -0.56, P < 0.0001), with female mice showing a greater effect. Females also showed an increase in relative organ weights at the highest test dose, in contrast to males where there was a slight decrease. A statistically significant increase in micronucleus frequency was seen in the bone marrow and spleen lymphocytes of both sexes, but only at the highest concentration. The short term repeated-dose study revealed a slight decrease in weight gain in both sexes, with a greater effect in females. It is concluded that phosphine is weakly genotoxic in both sexes of mice, and has an effect on weight gain. However, the weak genotoxic effect may not be biologically significant as it was seen only in the subchronic study and only at the highest test concentration of 4.5 +/- 0.8 ppm (approaching the LD50). Although such exposure conditions are unlikely to be encountered in an occupational environment, caution should continue to be exercised in the use of phosphine until more data become available.

show abstract

“…116 Likewise, 15,16-dihydroll-methylcyclopenta[a]phenanthren-17-one, a potent skin carcinogen, induced micronuclei in keratinocytes in vivo, whereas its non-carcinogenic unmethylated congener was inactive. 117 Moreover, B[a]P and DMBA showed transplacental induction of micronuclei in fetal liver of rodents; actually, the effects in fetal liver were stronger than those observed in maternal bone marrow. [118][119][120] Mutations in the hprt gene can be scored not only in some cell lines, but also in certain primary cells such as lymphocytes (isolated from blood or spleen).…”

Section: Genotoxicity In Mammalian Cells In Vivomentioning

confidence: 99%

Indicator Assays for Polycyclic Aromatic Hydrocarbon-Induced Genotoxicity

Glatt

2005

The Carcinogenic Effects of Polycyclic Aromatic Hydrocarbons

View full text Add to dashboard Cite

Tumorigenicity of cyclopenta[α]phenanthrene derivatives and micronucleus induction in mouse skin

Cited by 10 publications

References 0 publications

In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring

In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring

Determination of genotoxic and other effects in mice following short term repeated‐dose and subchronic inhalation exposure to phosphine

Indicator Assays for Polycyclic Aromatic Hydrocarbon-Induced Genotoxicity

Contact Info

Product

Resources

About