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alpha-Tocopherol & Ascorbic Acid /beta-carotene/reinoids

#C161A Effects of á-Tocopherol and Ascorbic Acid on the Production of â-Apo-carotenals and Retinoids from â-Carotene in the Lung Tissues of Cigarette Smoke-Exposed Ferrets in vitro.

Chun Liu, Robert M. Russell, Xiang-Dong Wang, USDA-HNRC at Tufts university, Boston, MA.

There are conflicting reports regarding the effects of beta-carotene on the risk of lung cancer between observational studies in which beta-carotene is mostly from fruits and vegetables and human beta-carotene intervention trials among heavy smokers.

A possible mechanism for the detrimental effect of beta-carotene supplementation in human trials is due to dosage and/or instability of beta-carotene in the antioxidant-poor environment (e.g., inadequate levels of beta-tocopherol and ascorbic acid) of the lungs of smokers.

Previously, we found that exposing ferrets to cigarette smoke enhanced oxidative excentric cleavage of beta-carotene in vitro. In the present study, we examined whether alpha-tocopherol, ascorbic acid, or both combined can prevent smoke-altered beta-carotene metabolism.

In vitro incubation of â-carotene with lung post-nuclear fractions from ferrets exposed to cigarette smoke was carried out in the absence or presence of alpha-tocopherol, ascorbic acid, or both vitamins. The oxidative cleavage metabolites of beta-carotene, beta-apo-carotenals (eta-apo-14', beta-apo-12', beta-apo-10', and beta-apo-8'), retinoic acid, and retinal were analyzed by HPLC.

The results showed that the formation of individual beta-apo-carotenals in smoke-exposed ferrets increased by approximately 2- to 6-fold as compared to control ferrets.

This smoke-enhanced production of individual beta-apo-carotenals was decreased by 36% to 75% when alpha-tocopherol (50 M) and ascorbic acid (50 micro-molar M) were added together into the incubation mixture.

Ascorbic acid alone had no effect on the inhibition of the formation of beta-apo-carotenals, while alpha-tocopherol alone had a modest effect. In contrast, the production of retinoic acid and retinal among smoke exposed ferrets was substantially increased (approximately 3 folds) when alpha-tocopherol combined with ascorbic acid was added into the incubation mixtures.

However, alpha-tocopherol alone or ascorbic acid alone only restored the smoke-reduced retinoic acid levels to those in control ferrets.

In conclusion, these data indicate that alpha-tocopherol and ascorbic acid acting together play an important role in preventing the enhanced oxidative excentric cleavage of beta-carotene induced by smoking exposure and facilitating the conversion of beta-carotene into retinoic acid and retinal.

(Supported by ACS grant #CNE-101107 and NIH grant #R01CA49195)

Frontiers in Cancer Prevention Research, 2003 AACR

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