Co-recombinogenic and anti-mutagenic effects of diethylhexylphthalate, inactiveness of pentachlorophenol in the spot test with mice

Fahrig, Rudolf; Steinkamp-Zucht, Angela

doi:10.1016/0027-5107(96)00036-x

Cited by 16 publications

(5 citation statements)

References 24 publications

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“…Moreover, the dipeptides did not have mutagenic activity when used alone, even at a high concentrations around of 10 mg/plate (data not shown). Together with Fahring's spot test [9], the present in vitro results indicate that the dipeptide combination can serve as an anti-mutagenic agent. Therefore, it seems that cyclic dipeptides having anti-mutagenic characteristics, have a potential as cancer chemo-preventive agents.…”

Section: Discussionmentioning

confidence: 83%

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Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and have anti-mutagenic properties

Rhee

2004

International Journal of Antimicrobial Agents

118

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Section: Discussionmentioning

confidence: 83%

“…2, and incubated for 16 h at 37 • C in a rotary incubator to ensure adequate aeration. Testing for anti-mutagenic activity was carried out using the pre-incubation method [9,10]. The positive mutagen used was 0.2 g of 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (AF-2, CAS No.…”

Section: Anti-mutagenic Activitymentioning

confidence: 99%

Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and have anti-mutagenic properties

Rhee

2004

International Journal of Antimicrobial Agents

118

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“…Also, DMBA-induced mouse mammary tumors showed LOH on chromosomes 4 (in 25% of the analyzed tumors), 8 (in 20%), and 11 (in 30%) (28). Moreover, ENU treatment has been shown to cause more frequently intragenic mutations than recombinational events at the Chinchilla locus by using the spot test in mice (29).…”

Section: Discussionmentioning

confidence: 99%

Carcinogen-induced loss of heterozygosity at the Aprt locus in somatic cells of the mouse

Wijnhoven

Sloun

Kool

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Genetic events leading to the loss of heterozygosity (LOH) have been shown to play a crucial role in the development of cancer. However, LOH events do not occur only in genetically unstable cancer cells but also have been detected in normal somatic cells of mouse and man. Mice, in which one of the alleles for adenine phosphoribosyltransferase (Aprt) has been disrupted by gene targeting, were used to investigate the potency of carcinogens to induce LOH in vivo. After 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) exposure, a 3-fold stronger mutagenic response was detected at the autosomal Aprt gene than at the X chromosomal hypoxantineguanine phosphoribosyltransferase (Hprt) gene in splenic T-lymphocytes. Allele-specific PCR analysis showed that the normal, nontargeted Aprt allele was lost in 70% of the DMBAinduced Aprt mutants. Fluorescence in situ hybridization analysis demonstrated that the targeted allele had become duplicated in almost all DMBA-induced mutants that displayed LOH at Aprt. These results indicate that the main mechanisms by which DMBA caused LOH were mitotic recombination or chromosome loss and duplication but not deletion. However, after treatment with the alkylating agent N-ethyl-N-nitrosourea, Aprt had a similar mutagenic response to Hprt while the majority (90%) of N-ethyl-N-nitrosoureainduced Aprt mutants had retained both alleles. Unexpectedly, irradiation with x-rays, which induce primarily large deletions, resulted in a significant increase of the mutant frequency at Hprt but not at Aprt. This in vivo study clearly indicates that, in normal somatic cells, carcinogen exposure can result in the induction of LOH events that are compatible with cell survival and may represent an initiating event in tumorigenesis.

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“…The loss could have occurred through simple deletion or a recombinational event; however, results with the autosomal Aprt gene of Aprt ϩ/Ϫ mice and Aprt ϩ/Ϫ humans indicate that the loss of the wild-type allele probably occurs as a consequence of mitotic recombination [Gupta et al, 1997;Van Sloun et al, 1998;Wijnhoven et al, 1998]. In addition to these results with the Tk gene, 10% of all Aprt mutants from ENU-treated Aprt ϩ/Ϫ mice contained LOH , and ENU has demonstrated recombinogenic activity in the mouse spot test [Fahrig and Steinkamp-Zucht, 1996].…”

Section: Tk Gene Of Tk ؉/؊ Mice Detects Loh Mutationmentioning

confidence: 99%

Molecular analysis of in vivo mutations induced by N‐ethyl‐N‐nitrosourea in the autosomal Tk and the X‐linked Hprt genes of mouse lymphocytes

Dobrovolsky

Chen

Heflich

1999

Environ. Mol. Mutagen.

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The endogenous, autosomal Tk gene is a potentially useful reporter of in vivo mutation since it may recover a wider range of mutational events than the X-linked Hprt gene or bacterial transgenes. In this study, we characterized mutations produced in the Tk gene of Tk(+/-) mice and compared them with mutations induced in the Hprt gene. Treatment of Tk(+/-) mice with N-ethyl-N-nitrosourea (ENU) resulted in dose-related increases in Tk mutants, as measured by the frequency of 5-bromodeoxyuridine-resistant (BrdUrd(r)) spleen lymphocytes. ENU-induced mutant frequencies in the Hprt gene, determined by measuring 6-thioguanine-resistant (TG(r)) lymphocytes, were similar to the Tk mutant frequencies. Allele-specific PCR of DNA from BrdUrd(r) lymphocyte clones suggested that 35% of clones from mice treated with ENU and 65% of clones from untreated animals had loss of heterozygosity (LOH) of the Tk gene due to deletion of the functional Tk allele. Reverse transcriptase-PCR/sequencing analysis of BrdUrd(r) and TG(r) clones from ENU-treated mice indicated that point mutations in both genes predominantly occurred at A:T basepairs; however, A:T-->G:C transition was the most common mutation in the Tk gene, while A:T-->T:A transversion was the most frequent mutation in the Hprt gene. Substitution at A:T basepairs in the Hprt gene occurred disproportionately with the mutated dT on the nontranscribed DNA strand, while this strand bias for mutation was not seen in the Tk gene. The results indicate that the specificity of ENU-induced point mutation differs between the two endogenous genes and that the autosomal Tk gene of Tk(+/-) mice is capable of recovering mutations caused by LOH. Environ. Mol. Mutagen. 34:30-38, 1999 Published 1999 Wiley-Liss, Inc.

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Co-recombinogenic and anti-mutagenic effects of diethylhexylphthalate, inactiveness of pentachlorophenol in the spot test with mice

Cited by 16 publications

References 24 publications

Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and have anti-mutagenic properties

Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and have anti-mutagenic properties

Carcinogen-induced loss of heterozygosity at the Aprt locus in somatic cells of the mouse

Molecular analysis of in vivo mutations induced by N‐ethyl‐N‐nitrosourea in the autosomal Tk and the X‐linked Hprt genes of mouse lymphocytes

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