Evaluation of structurally-related phenols for anti-photocarcinogenic and photoprotective properties.

Abstract

Abstract— Butylated hydroxytoluene (BHT) has previously been shown to provide protection against UV‐mediated erythema, carcinogenesis, and induction of epidermal ornithine decarboxylase (ODC). Butylated hydroxytoluene is but one compound of a class of organic chemicals, the phenols, that demonstrates antioxidant properties. On the basis of structural characteristics, the phenolic compounds butylated hydroxyanisole (BHA), propyl gallate, and vanillin were compared to BHT for antiphotocarci‐nogenic activity. SKH‐Hr‐1 female mice were fed diets containing 0.5% (wt/wt) BHT, BHA, vanillin or 0.3% propyl gallate. The animals received constant, daily (5 days/week) suberythemic levels of UVB radiation from Westinghouse BZS‐WLG lamps. Radiation was discontinued when 25 sunburn units (SBUs) had been delivered at week eleven. Animals were evaluated weekly for tumor latency and multiplicity. Of the four phenols tested, only BHT conveyed significant inhibition of both carcinogenic parameters—increasing latency by 5.2 weeks and reducing tumor multiplicity by 60%. Vanillin significantly reduced tumor multiplicity (48%). BHA and propyl gallate were without effect. Because ODC has been considered a requisite step in carcinogenesis, ODC activity was assayed to determine whether its induction might serve as a rapid screen for potential anti‐carcinogenic phenols. Animals were fed the respective phenol‐containing diets for two weeks, exposed to 0.45 J/cm/ of UVB from FS‐20 lamps, and epidermal extract assayed for ODC activity 28 h post‐irradiation. Both BHT and BHA significantly inhibited ODC induction, the former being most effective. Vanillin and propyl gallate were without effect. These data indicate that neither antioxidant or lipophilic properties, nor the tert‐butyl substituent common to both BHT and BHA, are sufficient determinants of anti‐photocarcinogenic activity. Nor does it appear that inhibition of ODC induction is an adequate indicator of such activity.