The initiation of tumours on mouse skin by dihydrodiols derived from 7,12‐dimethylbenz(a)anthracene and 3‐methylcholanthrene

Abstract

The cis-2a,3-diol and the trans-4,5-, trans-7,8-, trans-9,10- and trans-11,12-dihydrodiols of 3-methylcholanthrene and the trans-3,4, trans-5,6-, trans-8,9. and trans-10,11- dihydrodiols of 7,12-dimethylbenz[a]anthrancene have been tested, in comparison with the parent hydrocarbons, for their abilities to initiate skin tumours in female CDI mice. Groups of mice received a single topical application (25 micrograms) of a diol or of a hydrocarbon, and 1 week later repeated topical applications (1 microgram) of 12-0-tetradecanoylphorbol-13-acetate were commenced. The results show that the diol of 3-methylcholanthrene and the 3,4-diol of 7,12-dimethylbenz[a]anthrancene were active as initiating agents but that they were no more active than their parent hydrocarbon. The K-region 5,6-diol of 7,12-dimethylbenz[a]anthrancene, which cannot be converted directly into a vicinal diol-epoxide, was also active as a tumour-initiating agent when applied to mouse skin.

The molecular etiology and prevention of estrogen-initiated cancers

“…Tumor-initiating activity in mouse skin shows that the activity of the two diastereomeric 1-hydroxyMC-9,10-dihydrodiols is no greater than that of the parent compound MC (Chouroulinkov et al, 1979; Levin et al, 1979), while 1-hydroxyMC is less active than MC and the two 1-hydroxyMC-9,10-dihydrodiols. The proximate metabolite 1-hydroxyMC is also consistently much less carcinogenic than MC in mouse skin (Cavalieri et al, 1978; Sims, 1967) and rat mammary gland (Cavalieri et al, 1988d).…”

Revisão e atualização sobre carcinogênese química cutânea

“…Ao ser estudada a atividade tumorigênica de diversos metabólitos do MC na pele de camundongos CD-1, observou-se uma maior atividade com o hidroxi-9,10-dihidrodiol, apesar de que outros metabólitos também mostraram atividade superior ao MC 54 . Já outros autores, ao utilizar diversos dihidrodiois derivados de MC, em camundongos da mesma linhagem referida acima, acharam que o 9,10-dihidrodiol, embora tendo atividade iniciadora, não era, todavia, superior à obtida com o HAP de origem (55).…”

Stereoselective fungal metabolism of 7,12-dimethylbenz[a]anthracene: identification and enantiomeric resolution of a K-region dihydrodiol

“…7,12-Dimethylbenz[a]anthracene (7, (Fig. 1) has been one of the most intensely studied polycyclic aromatic hydrocarbons (PAHs), since it is recognized as one of the most potent carcinogens, when compared with other members of this class of chemicals (3,11,25,29,30). PAHs and their alkylated homologs are ubiquitous environmental pollutants and have been identified as by-products of coal gasification processes (16).…”