ETHANOL MODULATES METASTATIC POTENTIAL OF B16BL6 MELANOMA AND HOST RESPONSES

The experimental metastatic potential (lung-colonizing ability) of B16 BL6 melanoma cells was examined in C57BL/6 mice after exposure to etha nol in vitro and in vivo. In vitro, tumor cells were cultured with eth anol (0.3% v/v), or medium alone, for three passages at 5-day interval s. In vivo, B16BL6 melanoma was exposed to ethanol by administering et hanol (10% or 20% w/v) to mice following subcutaneous inoculation of t umor cells into the dorsal hip. All tumor cells were subsequently inoc ulated intravenously into the lateral tail Vein of water-drinking mice to assess changes in metastatic phenotype. Tumor cells cocultured in vivo with ethanol produced significantly higher numbers of superficial lung colonies, compared with tumor cells cultured in control medium. Experimental metastasis of tumor cells obtained from 20% w/v ethanol-c onsuming mice was also significantly increased, compared with cells ob tained from water-drinking mice, Metastasis of B16BL6 melanoma cells p reviously obtained from mice consuming 10% w/v ethanol did not differ from controls. In other experiments, water-drinking and ethanol-consum ing (2.5%, 10%, and 20% w/v) mice were inoculated subcutaneously into the dorsal hip with B16BL6 melanoma cells, and monitored for tumor gro wth rate and survival time. In these experiments, survival times were significantly shorter in mice consuming 20% ethanol, compared with all other groups. Subcutaneous tumor growth rate was unaffected by ethano l consumption. Lung metastasis resulting from subcutaneous tumor impla ntation of B16BL6 melanoma was respectively inhibited, or absent, in 1 0% and 20% ethanol-consuming groups. Thus, tumor growth rate and incid ence of lung metastases were not apparent determinants of decreased su rvival in 20% ethanol-consuming mice. The results of this study indica te that the experimental metastatic potential of B16BL6 melanoma is in creased during exposure to ethanol; however, metastasis from subcutane ous tumor-bearing mice is suppressed. This latter finding is consisten t with previous results in which spontaneous metastasis was also suppr essed after inoculation of the tumor into the pinna of the ear. Althou gh ethanol increases the ability of B16BL6 melanoma to colonize the lu ng after intravenous inoculation, this effect is abated in the presenc e of host factors in ethanol-consuming mice.