7,12-Dimethylbenz[a]anthracene

About: 7,12-Dimethylbenz[a]anthracene is a research topic. Over the lifetime, 1717 publications have been published within this topic receiving 40892 citations.

Increased in Vitro Growth Capacity of Tracheal Epithelium Exposed in Vivo to 7,12-Dimethylbenz(a)anthracene

Abstract: Heterotopic tracheal transplants of rats were exposed in vivo to 150 or 640 microng of 7, 12-dimethylbenz(a)anthracene (DMBA) delivered over 2 weeks, and the epithelium was studied in vitro in an attempt to identify changes in growth behavior during early phases of neoplastic development Explants were made from the exposed tracheas, as well as from a series of controls, and the rate of epithelial outgrowth from the explants was measured Secondly, the capacity of the outgrowths to survive as primary cultures and their ability to survive multiple in vitro passages were studied During the initial planting, the rate of outgrowth was by far the greatest from the explants preexposed to 150 microng DMBA Outgrowth from explants preexposed to 640 microng DMBA was sparse during the first planting but increased markedly during repeated planting when insulin- and hydrocortisone-supplemented medium was used Establishment of outgrowth during repeated planting of carcinogen-exposed tracheal pieces was clearly hormone dependent Control explants did not exhibit this hormone dependency Primary cultures could be established from only three of six explants preexposed to 150 microng DMBA These explants had been initiated in insulin- and hydrocortisone-supplemented medium The primary cultures were successfully subcultured Primary cultures were also established from five of five explants preexposed to 640 microng DMBA and cultured in hormone-supplemented medium At least one cell line was obtained from each of the explants To establish and maintain primary cultures from control tracheas required an enriched medium containing amino acid supplements, sodium pyruvate, and putrescine, as well as the hormone supplements However, such cultures could not be subcultured The primary cultures from the carcinogen-exposed explants and the subsequently developed cell lines all exhibited morphological characteristics of keratinizing squamous epithelium These characteristics include: epithelioid cell morphology, multilayering and sloughing of orangeophilic squamous cells, and the presence of keratohyalin granules These experiments demonstrate a markedly increased in vitro growth capacity of tracheal epithelium after a short in vivo exposure to carcinogen

3-methylcholanthrene And 7,12-dimethylbenz[a]anthracene in mouse skin.

Abstract: The metabolic activation of the polycyclic hydrocarbons benzo [a] pyrene and 7-methylbenz [a] anthracene in mouse skin appears to involve the formation of vicinal diol-epoxides [l] that react with nucleic acids in this tissue [2-51. This mechanism of activation may be a general one for this class of chemical carcinogens and efforts are now being made to extend the hypothesis to include other hydrocarbons. The examination, using photon-counting spectrofluorimetry, of nucleic acids isolated from tis’sues treated in vivo with polycyclic hydrocarbons, has already proved to be of value in identifying the sites of activation in benzo [a] pyrene [2] and in 7-methylbenz [a] anthracene [4,6] . In this paper we present data from fluorescence studies obtained with the potent carcinogens 3-methylcholanthrene (I) and 7,12-dimethylbenz[a] anthracene (II). These data show that the hydrocarbon moieties, bound to the DNA of mouse skin treated in vivo with either of the parent hydrocarbons, have spectral characteristics consistent with the retention of a substituted anthracene nucleus in

Carcinogenicity of derivatives of 7,12-dimethylbenz(a)anthracene.

Abstract: Summary Eleven derivatives of 7,12-dimethylbenz(a)anthracene were tested for carcinogenicity in Sprague-Dawley female rats by the s.c. injection of 1.0 or 0.1 mg of compound dissolved in 0.1 ml of sesame oil on alternate days for 20 doses. Eight derivatives [7-hydroxymethyl-12-methyl-, 7-formyl-12-methyl-, 7-methoxymethyl-12-methyl-, 7-acetoxymethyl-12-methyl-, 7-benzoyloxymethyl-12-methyl-, 7-iodomethyl-12-methyl-, 7-bromomethyl-12-methyl,- and 7-chloromethyl-12-methylbenz(a)anthracene] were carcinogenic at the 1-mg dose level, and 5 [benzoyloxymethyl-12-methyl-, 7-formyl-12-methyl-, 7-bromomethyl-12-methyl-, 7-hydroxymethyl-12-methyl-, and 7-iodomethyl-12-methylbenz(a)anthracene] were carcinogenic at the 0.1-mg dose level (200 days of observation). These observations suggest that the formation of 7-hydroxymethyl-12-methylbenz(a)anthracene may be the first step in the chain of events which result in cancer caused by these polycyclic hydrocarbons.

Role of Ultraviolet Radiation in the Induction of Melanocytic Tumors in Hairless Mice following 7,12-Dimethylbenz(a)anthracene Application and Ultraviolet Irradiation

Abstract: We examined the role of UVR (UV radiation) (UVA, 320–400 nm; UVB, 290–320 nm; and the combination of UVA and UVB) as a promoter in the induction of cutaneous melanoma. One hundred and seventy hairless mice (Skh-hr2), 6–8 weeks old, were treated in 8 groups: group I, DMBA [7,12-dimethylbenz( a )anthracene] plus UVA; group II, DMBA plus UVA plus UVB; group III, DMBA plus UVB; group IV, DMBA; group V, UVA; group VI, UVA plus UVB; group VII, UVB; group VIII, control. DMBA (0.5% solution) was applied once to promote the formation of dermal melanocytic nevus-like lesions while UVR treatments were conducted 3 times/week for 30 weeks. The mice were examined periodically for the development of multiple pigmented lesions, papillomas, squamous cell carcinomas, melanomas, and lymphomas. Treatment with DMBA plus UVA, DMBA plus UVB, and DMBA plus UVA plus UVB stimulated the development of multiple pigmented nevus-like lesions (85–100%) in mice of groups I, II, III, and IV. Upon necroscopy, 27–33% of animals in groups I, II, and III receiving UVR treatments developed clinically and histologically characterized melanomas. Treatment with DMBA alone did not produce melanomas. DMBA-treated animals in groups I, II, and III which received UVR treatments also developed lymphomas (21–50%). Animals treated with DMBA alone or those that received UVB or the combination of UVB plus UVA (without DMBA) developed only papillomas and squamous cell carcinomas (25–47%). Skin tumors were analyzed for the presence of point mutations in the ras gene. Polymerase chain reaction amplification of DNA and selective oligonucleotide hybridization revealed mutations in the 61st codon of the N- ras gene in the precursor nevus-like lesions and melanoma samples studied. This study suggests that UVR (both UVA and UVB) plays a role as a promoter in the stimulation of melanoma and lymphoma development in hairless mice.