Uptake of 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene in melanin-containing tissues.
It is widely accepted that UV exposure is the main etiological factor for malignant melanoma. Epidemiologic studies, however, have indicated that also chemical carcinogens may be a risk factor for the disease. Polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene represent an important class of carcinogenic chemicals. It is known that 7,12-dimethylbenz(a)anthracene can induce melanotic tumours in various animal species, and human melanocytes in culture have been found to be capable of metabolizing benzo(a)pyrene to its proximate carcinogen benzo(a)pyrene-7,8-diol. In the present study the disposition of 14C- and 3H-7,12-dimethylbenz(a)anthracene and 14C-benzo(a)pyrene was studied in pigmented and albino mice and Syrian golden hamsters by whole-body autoradiography. The results showed pronounced retention of label in the melanin-containing structures of the eyes and the hair follicles in the pigmented animals. The labelling of the corresponding structures in the albino animals was low. Additional experiments showed that 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene as well as some of their metabolites are bound to melanin in vitro. The specific localization of the polycyclic aromatic hydrocarbons in pigmented tissues due to melanin affinity, combined with bioactivating capacity of melanocytes, suggest that these substances may play a role in the induction of malignant melanoma.
Roberto
A
A
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
Larsson
B S
BS
Tjälve
H
H
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000633:toxicity*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D006224:Cricetinae; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D002273:Carcinogens; D008543:Melanins; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene