Generalized Cutaneous Hyperpigmentation in Hairless Mice Induced by Topical Dimethylbenzanthracene

Abstract

The skin of hairless (Ng/Bln) mice topically treated with dimethylbenzanthracene (DMBA) was investigated by light microscopy, histochemistry, electron microscopy and autoradiography in order to gain some insight into the mechanisms by which the DMBA-induced cutaneous hyperpigmentation is mediated. The results of the present study indicate that this phenomenon is due to the DMBA-induced stimulation of both the tyrosinase system and the mitotic activity of dopa-inactive dormant melanocytes.

The Neurofibromatosis Type 1 (Nf1) Tumor Suppressor is a Modifier of Carcinogen-Induced Pigmentation and Papilloma Formation in C57BL/6 Mice

“…We challenged Nf1 mutant mice with DMBA; topical application of DMBA induces patches of pigmentation in susceptible strains of mice (Klaus and Winkelmann, 1965). DMBA-treated skin shows increased proliferation of normally dormant DOPA-inactive melanocytes and enhanced melanogenic activity (Tsambaos et al, 1989); melanin is transferred to adjacent keratinocytes leading to visible pigmentation. We also challenged Nf1 mutant mice in the two-stage carcinogenesis model, in which skin is initiated with a potent carcinogen like DMBA and then exposed to multiple treatments with a tumor promoter such as wounding or TPA (Deelman, 1927;DiGiovanni, 1992).…”

Induction of Melanogenic Abnormalities in NF1+/– Mutant Mice by DMBA

“…In summary, nine of nine (100%) NF1+/± mice had either type of abnormality compared with two of 10 (20%) wild-type mice (Table I). DMBA has been found to induce melanogenesis in several experimental models (Kanno et al, 1986(Kanno et al, , 1987Tsambaos et al, 1989), and is taken up by melanin-containing tissues (Roberto et al, 1996). It has been demonstrated to be mitogenic and to stimulate tyrosinase in DOPA-inactive melanocytes (Tsambaos et al, 1989), which subsequently synthesize melanin.…”

“…DMBA has been found to induce melanogenesis in several experimental models (Kanno et al, 1986(Kanno et al, , 1987Tsambaos et al, 1989), and is taken up by melanin-containing tissues (Roberto et al, 1996). It has been demonstrated to be mitogenic and to stimulate tyrosinase in DOPA-inactive melanocytes (Tsambaos et al, 1989), which subsequently synthesize melanin. DMBA induced melanogenesis in only one wild-type mouse but in almost all mutant mice, indicating a differential sensitivity due to the loss of neuro®bromin.…”