Effect of caloric restriction on aflatoxin B1-DNA adduct formation and associated factors in Fischer 344 rats: Preliminary findings

Effect of dietary macronutrients on aflatoxicosis: a mini‐review

“…The dietary restriction of carbohydrate decreases CYP450‐mediated AFB 1 epoxidation and increases the binding of AFB 1 ‐8,9‐epoxide to low‐molecular‐weight compounds such as glutathione involved in the detoxification process of AFB 1 . These findings confirmed the preliminary results published earlier . The authors found that caloric restriction decreased the macromolecular binding of AFB 1 that may be attributable to the metabolic alteration of aflatoxicosis in rats …”

“…17 These findings 16,17 confirmed the preliminary results published earlier. 18 The authors found that caloric restriction decreased the macromolecular binding of AFB 1 that may be attributable to the metabolic alteration of aflatoxicosis in rats. 18…”

Calorie restriction modulates chemically induced in vivo somatic mutation frequency

“…These data suggest that caloric restriction either affects metabolic activation and or detoxification of A m l , decreasing the genomic DNA adduct burden, or beneficially alters DNA repair, reducing the potential of replicating DNA containing AFB 1 mutagenic lesions. It is well established that CR affects a plethora of physiological functions including DNA repair [Lipman et al, 19891, metabolism of xenobiotics [Manjgaladze et al, 19931, oncogene expression [Nakamura et al, 19891, as well as lifespan and spontaneously occurring neoplasms [Weindruch, 19911. With regard to AFB, in the rat, we have previously shown that CR reduced metabolic activation to a DNA reactive species by more than 50% [Pegram, et al, 1989;Chou, et al, 19911 and increased glutathione S-transferase activity [Chen et al, 19951, a phase I1 enzyme responsible for detoxification of AFB I -epoxide. Additionally, we have shown that hepatocytes derived from CR rats on the same diet regimen as reported in the present paper had reduced AFB I -induced unscheduled DNA synthesis, a measurement of DNA repair, substantiating the reduced DNA adduct burden when compared to the AL counterparts [Shaddock et al, 19931.…”

“…Although the mechanisms underlying the inhibitory effect are still not evident, a variety of hypotheses have been proposed that generally focus on the promotion stage of carcinogenesis [Fu et al, 19941. Recent reports, however, indicate that CR can modulate xenobiotic metabolism and DNA binding, suggesting that, in addition to promotion, the initiation stage of the carcinogenesis process can be significantly inhibited [Pegram et al, 1989;Chou et al, 1993;Chen et al, 19951. Our recent work has shown that CR reduces the binding of the potent hepatocarcinogen aflatoxin B, (AFB,) to DNA of rats exposed in vivo [Chou et al, 19931 and from isolated hepatocytes exposed in vitro [Shaddock et al, 19931. Mutations have been implicated in the etiology of cancer [Fearon and Vogelstein, 19901 and are thought to be important in the aging process as well as in the induction of a large number of diseases. The measurement of this biological endpoint is used to predict the genotoxic risk associated with potential environmental toxicants.…”

The MDT-15 Subunit of Mediator Interacts with Dietary Restriction to Modulate Longevity and Fluoranthene Toxicity in Caenorhabditis elegans

“…In addition to the positive effects of DR on longevity, several studies in rodents have examined the effects of DR or short-term starvation on resistance to environmental toxins [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50]. One particularly interesting recent report suggests that short-term fasting is sufficient to confer striking resistance to a lethal dose of the chemotherapy drug etoposide [51].…”