Review of chemical and uv light‐induced melanomas in experimental animals in relation to human melanoma incidence

Abstract

In a few epidemiological studies on oil refinery workers, a slight excess of melanoma incidence has been reported. To see if this might be linked to exposure to polycyclic aromatic hydrocarbons (PAHs) contained in refinery streams, a review of animal data on the relationship between PAH exposure, UV light and melanoma induction has been carried out and compared with human data. This revealed that the highly carcinogenic PAH 7,12-dimethylbenz[a]anthracene (DMBA) was capable of inducing melanomas in hamsters, mice and guinea pigs, but only under certain experimental conditions. Evidence suggested that other carcinogenic PAHs were unable to induce melanomas. As high dose levels of DMBA were generally required to produce melanomas, it was not considered that the amounts present in refinery streams would be sufficient to account for an increase in melanoma incidence in exposed workers. This conclusion was substantiated by the failure of petroleum-derived complex hydrocarbon mixtures to produce melanomas in animals or man and by drawing attention to the absence of any association between melanoma incidence and the incidence of other skin cancers in man. If PAHs were responsible for an increase in melanoma incidence, an increase in other skin tumours would also be expected. It was concluded that animal data, taken in conjunction with other information, do not suggest that PAH exposure is likely to be the cause of any elevation in melanoma incidence in refinery workers. More detailed epidemiological findings would be required to establish whether any excess incidence of melanomas was due to sunlight, other risk factors or chance occurrences.

Nonsolar occupational risk factors for cutaneous melanoma

“…Possible mechanisms for an effect of PAHs, in particular DMBA, on cutaneous melanoma are as follows: (i) PAHs act as a competitive inhibitor of the enzyme tyrosinase, which is responsible for melanin synthesis; and/or (ii) PAHs lead to the generation of superoxide radicals in the presence of UVR, causing DNA cleavage 74 . Laboratory experiments with DMBA can induce melanoma in both mice and hamsters, 75 and its effects are exacerbated by sunlight 76 . Benzene toxicity may be related to the formation of its metabolites: hydroquinone, phenols, and catechols.…”

Ecotropic C-type retrovirus of B16 melanoma and malignant transformation of normal melanocytes

“…Later experiments showed that a single skin application of DMBA followed by prolonged (6-12 months) application of croton oil is the most efficient method for melanoma induction, resulting in development of melanomas in 15-20% of treated mice (Berkelhammer and Oxenhandler, 1987;Shapiro et al, 1996). In contrast to DMBA, other carcinogenic polycyclic aromatic hydrocarbons were inefficient at melanoma production (Ingram, 1992). The precise mechanisms and genetic basis of melanoma formation in mice and humans remain mostly unclear.…”

Induction of neoplastic cells in rat skin

“…The experiment got satisfactory outcome for skin melanoma in rats, hamsters, and Guinea pigs, but only when DMBA and UVR-B were applied in high doses, disregarding the relationship of refinery workers exposure with high incidence of melanoma, because researchers found that the workers were exposed only a small fraction of thishydrocarbon 24 . Yang 25 reports high toxicity of polycyclic aromatic hydrocarbons in fuels human skin.…”