Details

Autor(en) / Beteiligte

• Wang, Yongyin
• Gao, Dayuan
• Atencio, David P.
• Perez, Evangeline
• Saladi, Rao
• Moore, Julian
• Guevara, Denise
• Rosenstein, Barry S.
• Lebwohl, Mark
• Wei, Huachen

Titel

Combined subcarcinogenic benzo[a]pyrene and UVA synergistically caused high tumor incidence and mutations in H‐ras gene, but not p53, in SKH‐1 hairless mouse skin

Ist Teil von

• International journal of cancer, 2005-08, Vol.116 (2), p.193-199

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2005

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Combined subcarcinogenic doses of benzo[a]pyrene (BaP) and UVA induced H‐ras, but not p53, gene mutations 8 weeks before tumor emergence in SKH‐1 mice. Neither UVA (40 kJ/m2) nor BaP (8 nmol) induced any tumors after mice were topically treated 3 times/week for 25 weeks. However, combined BaP‐UVA treatment synergistically increased tumor incidence and multiplicity. All tumors induced by BaP‐UVA were malignant. The epidermis was collected from mice treated for 2, 6 and 10 weeks. DNA from UVB‐ (0.3 kJ/m2) or BaP‐UVA‐(8 nmol and 40 kJ/m2‐induced tumors was isolated and screened for H‐ras and p53 mutations. Four types of point mutation, GGC→GAC, GCC, GTC and CGC, occurred in UVB‐induced tumors at H‐ras codon 13; and one type of point mutation, GGA→GAA, at codon 12. Treatment with either BaP alone or BaP‐UVA for 10 weeks caused GGA→GAA mutation at codon 12 or GGC→GAC mutation at codon 13 in nontumor skin, respectively, as well as in tumors induced by BaP‐UVA. All of the 10‐week samples treated with either BaP or BaP‐UVA showed detectable mutations at codons 12 and 13, but the genetic load was significantly higher in BaP‐UVA‐treated mice than in those exposed only to BaP. UVA alone induced mutations at codon 12 in only one‐third of samples. G→A mutations induced by BaP or BaP‐UVA at position 38 of codon 13 have not been reported previously. C→T transitions were detected in p53 hot spots of exon 8 in 2 of 19 BaP‐UVA‐induced tumors but were not found in nontumor skin. © 2005 Wiley‐Liss, Inc.