Inhibition of benzoyl peroxide-mediated tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated skin of Sencar mice by antioxidants nordihydroguaiaretic acid and diallyl sulfide.
Benzoyl peroxide (BPO), a free radical generating compound, is widely used in topical medications prescribed for acne vulgaris and in cosmetic products. It has been shown to possess tumor-promoting activity in murine skin initiated with chemical carcinogens such as 7,12-dimethylbenz(a)anthracene (DMBA). In the present study we assessed the effect of the antioxidants nordihydroguaiaretic acid (NDGA) and diallyl sulfide (DAS) against BPO-mediated tumor promotion in murine skin. Pretreatment of Sencar mice with NDGA and DAS prior to skin application of BPO resulted in a time- and dose-dependent inhibition of epidermal ODC induction caused by BPO. Tumor initiation was achieved by a single topical application of DMBA (10 micrograms/animal) to Sencar mice. Ten days later tumor promotion was begun by twice-weekly topical application of BPO (20 mg/animal). The anticarcinogenic effects of NDGA (25 mumol/mouse) and DAS (20 mumol/mouse) were evaluated by administering these agents topically 60 min prior to each BPO application. After 26 weeks on test, the number of benign papillomas/mouse were 0.10 +/- 0.07 and 2.15 +/- 0.30 in the NDGA and DAS pretreated group of animals as compared to 4.40 +/- 1.14 in animals receiving BPO alone. After 51 weeks on test, the number of squamous cell carcinomas/mouse were 0.00 +/- 0.00, 0.35 +/- 0.10 in the NDGA and DAS pretreated group of animals as compared to 0.65 +/- 0.12 in animals receiving BPO alone. From these data we suggest that the antioxidants NDGA and DAS can abrogate the tumor-promoting effects of BPO in murine skin and that NDGA is substantially more effective than DAS in this regard.
Athar
M
M
Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, Ohio.
Raza
H
H
Bickers
D R
DR
Mukhtar
H
H
D015127:9,10-Dimethyl-1,2-benzanthracene; D000498:Allyl Compounds; D000818:Animals; D001585:Benzoyl Peroxide / Q000494:pharmacology*; D002273:Carcinogens; D002396:Catechols / Q000627:therapeutic use*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D009637:Masoprocol / Q000627:therapeutic use*; D051379:Mice; D065108:Ornithine Decarboxylase Inhibitors; D010545:Peroxides / Q000494:pharmacology*; D012867:Skin / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013440:Sulfides / Q000627:therapeutic use*
D000498:Allyl Compounds; D002273:Carcinogens; D002396:Catechols; D065108:Ornithine Decarboxylase Inhibitors; D010545:Peroxides; D013440:Sulfides; D015127:9,10-Dimethyl-1,2-benzanthracene; C038491:allyl sulfide; D009637:Masoprocol; D001585:Benzoyl Peroxide