Long-term Cancer Bioassays of Ascorbic Acid

Abstract

Kuroiwa et al. [2008] report on the lack of carcinogenesis of coadministration of ascorbic acid and sodium nitrite in male F344 rats, despite causing oxidative DNA damage-associated mutagenicity in vitro and increased levels of 8-hydroxydeoxyguanosine in rat forestomach epithelium. Earlier studies showed forestomach carcinogenesis was enhanced by this combination after initiation with N-methyl-N'-nitro-N-nitrosoguanidine [Okazaki et al., 2006], and forestomach papillomas were induced without prior initiation, using sodium nitrite and sodium ascorbate (Yoshida et al., 1994). Ascorbic acid enhanced butylated hydroxyanisole [BHA]-induced forestomach lesions [Shibata et al., 1993], sodium L-ascorbate following initiation with several nitrosamines inhibited liver but promoted renal pelvis and bladder carcinogenesis [Thamavit et al., 1989], and sodium ascorbate but not ascorbic acid induced neoplastic and preneoplastic lesions of the urinary bladder [Fukushima et al., 1986], implicating the influence of the sodium ion and increased pH on bladder carcinogenesis. Following initiation with 1,2-dimethylhydrazine, sodium Lascorbate increased the incidence of adenomas and the number of tumors per rat of the colon (especially of the distal colon) [Shirai et al., 1985]. Ito et al. [1983, 1986] posed that antioxidants have different effects (promoting or inhibitory influences) depending on the organ studied and suggest the importance of a whole body approach to their investigation.