Mouse skin melanoma induced in two stage chemical carcinogenesis with 7, 12-dimethylbenz[a]anthracene and croton oil

Abstract

Mouse skin melanomas were induced in two stage skin carcinogenesis with 7,12-dimethylbenz[a]anthracene as initiator and croton oil as promoter. After approximately 25 weeks of promotion, small black macules of the skin were observed in C57BL, CDF1 and BDF1 mice, and progressively grew with time. Macules less than 2 mm in diameter were localized mostly in the lower portion of the dermis and, histologically, these lesions were consistent with the diagnosis of melanocytoma and were composed of polygonal to round cells loaded with large numbers of melanin granules. The cells were closely packed forming well-demarcated cell-nests with occasional columnar arrangement. In the macules over 2 mm in diameter, the cells were closely packed to form irregularly bordered cell-nests, showing invasive growth into the surrounding tissues. The lesions were diagnosed as malignant melanomas. The incidence of benign and/or malignant melanoma differed among strains: 80% in BDF1, 70% in CDF1, 30% in C57BL/6 and 0% in DBA/2 mice. One example of tumor induced in a CDF1 mouse was transplantable to homologous CDF1 mice.

Development of Early Melanocytic Lesions in Transgenic Mice Predisposed to Melanoma

“…melanocytes is increased at all anatomical sites to which neural-crest-derived melanocytes normally migrate. Clonal ex-Key words: Insertion mutagenesis, Melanocytes, Spontaneous pansion and morphological changes of these melanocytes can skin lesion be detected as early as postnatal day (PND) 15…”

“…Newborn pups of transgenic mice and non-transgenic littermates were sacrificed on PND 1,3,5,7,9,11,13,15,or 30. Transgenic mice were identified by Southern blot hybridization of genomic DNA to the inserted transgene Clone B (16).…”

“…Two to four of transgenic mice and non-transgenic litter mates were examined at PND 1,3,5,7,9,11,13,15,and 30. Dendritic melanocytes were found in the spleen of one non-transgenic and one transgenic mouse at PND 5, and one non-transgenic mouse at PND 7.…”

“…The increasing incidence of melanoma and its high mortality underscore the need to improve methods of prevention, diagnosis, and treatment. At present, few animal models of melanoma are available, the majority of which require either the insertion of an exogenous oncogene driven by a tissue-specific or viral promoter and/or treatment of the animals with chemical carcinogens or ultraviolet light (UV) (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). these transgenic mice, histological assessment was performed in mice ranging in age from postnatal day (PND) 1-30.…”

A retrospective mortality study within operating segments of a petroleum company

“…Most refinery worker cohort studies do not show an excess of skin cancer and/or melanoma [Delzell et al, 19881, except for two [Rushton and Alderson, 1981;Nelson et al, 19871. In experimental studies, 7,12-dimethylbenz(a)anthracene (DMBA) [Takizawa et al, 1985;Berkelhammer and Oxenhandler, 19871 and urethane [Vesselinovitch et al, 1970;Toth et al, 19611 have been shown to cause melanomas in mice and hamsters, respectively. In summary, however, the literature lends little support that hydrocarbon streams encountered in the upstream operating segment can cause melanoma.…”