Mutagenicity of dihydroxybenzenes and dihydroxynaphthalenes for Ames Salmonella tester strains

Hakura, Atsushi; Tsutsui, Yoshie; Mochida, Hisatoshi; Sugihara, Yoshiki; Mikami, Takashi; Sagami, Fumio

doi:10.1016/s0165-1218(96)90118-4

Cited by 22 publications

(5 citation statements)

References 13 publications

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“…However, in the presence of a compromised stress response, caused perhaps by the inhibition of key repair enzymes, the damage cannot be effectively repaired and the cell dies. in mouse cells in vivo (44), it causes base-pair changes in the TA1535 Salmonella tester strain (45) and is mutagenic in oxidant-sensitive (TA104) Salmonella tester strains (46), consistent with the mutagenicity of 1,4benzoquinone in several Ames bacterial tester strains (47). Hydroquinone also causes renal tubular cell degeneration in the renal cortex of male and female rats (F344/N) treated for 13 weeks with hydroquinone (1.82 mmol/kg) (48), and in long-term studies it causes marked increases in tubular cell adenomas (48,49).…”

Section: Role Of Polyphenolic-glutathionementioning

confidence: 99%

Biological Reactivity of Polyphenolic−Glutathione Conjugates

Monks

Lau

1997

Chem. Res. Toxicol.

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Section: Role Of Polyphenolic-glutathionementioning

confidence: 99%

Biological Reactivity of Polyphenolic−Glutathione Conjugates

Monks

Lau

1997

Chem. Res. Toxicol.

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“…Although HQ is generally not mutagenic in short-term bacterial mutagenicity assays (9,10), and no mutagenic activity has been found in mouse cells in vivo (11), HQ causes base pair changes in the TA1535 Salmonella typhimurium test strain (12) and is mutagenic in oxidantsensitive (TA104 and TA2637) Salmonella test strains (13), consistent with the mutagenicity of 1,4-benzoquinone in several Ames bacterial test strains (14). HQ is also clastogenic and induces sister chomatid exchange (4,12,15), catalyzes the in vitro formation of 8-oxode- oxyguanosine (16,17), and causes single-strand DNA breaks in isolated hepatocytes (18).…”

Section: Introductionmentioning

confidence: 99%

Carcinogenicity of a Nephrotoxic Metabolite of the “Nongenotoxic” Carcinogen Hydroquinone

Lau

Monks

Everitt

et al. 2000

Chem. Res. Toxicol.

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Hydroquinone (HQ) is a potential human carcinogen to which many people are exposed. HQ generally tests negative in standard mutagenicity assays, making it a "nongenotoxic" carcinogen whose mechanism of action remains unknown. HQ is metabolized to 2,3,5-tris(glutathion-S-yl)HQ (TGHQ), a potent toxic and redox active compound. To determine if TGHQ is a carcinogen in the kidney, TGHQ was administered to Eker rats (2 months of age) for 4 or 10 months. Eker rats carry a germline mutation in the tuberous sclerosis 2 (Tsc-2) tumor suppressor gene, which makes them highly susceptible to the development of renal tumors. As early as 4 months after the initiation of treatment (2.5 micromol/kg, i.p.), TGHQ-treated rats developed numerous toxic tubular dysplasias of a form rarely present in vehicle-treated rats. These preneoplastic lesions are believed to represent early transformation within tubules undergoing regeneration after injury by TGHQ, and adenomas subsequently arose within these lesions. After treatment for 10 months (2.5 micromol/kg for 4 months followed by 3.5 micromol/kg for 6 months), there were 6-, 7-, and 10-fold more basophilic dysplasias, adenomas, and renal cell carcinomas, respectively, in TGHQ-treated animals than in controls. Most of these lesions were in the region of TGHQ-induced acute renal injury, the outer stripe of the outer medulla. Loss of heterozygosity (LOH) at the Tsc-2 locus was demonstrated in both the toxic tubular dysplasias and tumors from rats treated with TGHQ for 10 months, consistent with TGHQ-induced loss of tumor suppressor function of the Tsc-2 gene. Thus, although HQ is generally considered a nongenotoxic carcinogen, our data suggest that HQ nephrocarcinogenesis is probably mediated by the formation of the quantitatively minor yet potent nephrotoxic metabolite TGHQ, which induces sustained regenerative hyperplasia, loss of tumor suppressor gene function, and the subsequent formation of renal adenomas and carcinomas. In addition, our data demonstrate that assumptions regarding mechanisms of action of nongenotoxic carcinogens should be considered carefully in the absence of data on the profiles of metabolites generated by these compounds in specific target organs for tumor induction.

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“…In that way, both substances could replace kojic acid on topical whitening formulations, ensuring a similar performance but in a safer way. Kojic acid and hydroquinone were longer reported to be mutagenic on bacterial systems (AMES test) [33][34][35], whereas S. terebinthifolius extract was demonstrated to be inert on this model, as well as reported to linoleic acid [28,29].…”

Section: Discussionmentioning

confidence: 91%

Schinus terebinthifolius Raddi extract and linoleic acid from Passiflora edulis synergistically decrease melanin synthesis in B16 cells and reconstituted epidermis

Jorge

Arroteia

Santos

et al. 2012

Intern J of Cosmetic Sci

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Several treatments for skin whitening are available today, but few of them are completely adequate, especially owing to the carcinogenic potential attributed to classical drugs like hydroquinone, arbutin and kojic acid. To provide an alternative and safer technology for whitening, we developed two botanical compounds originated from Brazilian biodiversity, an extract of Schinus terebinthifolius Raddi and a linoleic acid fraction isolated from Passiflora edulis oil. The whitening effect of these compounds was assessed using biochemical assays and in vitro models including cellular assays and equivalent skin. The results showed that S. terebinthifolius Raddi extract is able to reduce the tyrosinase activity in vitro, and the combination of this extract with linoleic acid is able to decrease the level of melanin produced by B16 cells cultured with melanocyte-stimulating hormone. Furthermore, melanin was also reduced in human reconstituted epidermis (containing melanocytes) treated with the compounds. The combination of the compounds may provide a synergistic positive whitening effect rather than their isolated use. Finally, we demonstrated that the performance of these mixed compounds is comparable to classical molecules used for skin whitening, as kojic acid. This new natural mixture could be considered an alternative therapeutic agent for treating hyperpigmentation and an effective component in whitening cosmetics.

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Mutagenicity of dihydroxybenzenes and dihydroxynaphthalenes for Ames Salmonella tester strains

Cited by 22 publications

References 13 publications

Biological Reactivity of Polyphenolic−Glutathione Conjugates

Biological Reactivity of Polyphenolic−Glutathione Conjugates

Carcinogenicity of a Nephrotoxic Metabolite of the “Nongenotoxic” Carcinogen Hydroquinone

Schinus terebinthifolius Raddi extract and linoleic acid from Passiflora edulis synergistically decrease melanin synthesis in B16 cells and reconstituted epidermis

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