Possible Carcinogenic Mechanisms Underlying Renal Carcinogens in Food

Abstract

Some chemicals contained in foods originating from a variety of sources including natural plants, food additives, residual pesticides, mycotoxins and by-products created during food processing and/or cooking have previously been demonstrated to be carcinogenic at various sites in rodents. This review focuses on reported renal carcinogens in natural products such as d-limonene and aristolochic acid (AA), food additives such as potassium bromate (KBrO 3 ) and madder color (MC), as well as mycotoxins such as ochratoxin A (OTA) and citrinin (CTN) and discusses data from reporter gene mutation assays. In addition to in vivo genotoxicity, recent information on several factors related to chemical carcinogenesis, such as DNA modifications and cell proliferation, gave insight into possible modes of action that underlie renal carcinogenesis. Given that neither d-limonene nor CTN induced increases in mutant frequencies (MFs) in some reporter genes, cell proliferation at target sites arising from compensatory and/or direct mitogenic action may play a key role in the carcinogenic mechanism of these compounds. Clear positive results from reporter gene mutation assays for AA, MC and OTA strongly suggest that genotoxic mechanisms are involved in carcinogenesis induced by these agents. While KBrO 3 elevated MFs in the red/gam gene (Spi − ), it did so to a lower extent than did potent genotoxic carcinogens. Accordingly, the participation of genotoxic mechanisms in KBrO 3 -induced renal carcinogenesis may be limited.

Mechanism of Error-Free DNA Replication Past Lucidin-Derived DNA Damage by Human DNA Polymerase κ

“…Misincorporations caused by translesion synthesis across LdG by major TLS DNA polymerases tested here are T or G by pol η and T by pol ι (Figure 2B and Table S2 of the Supporting Information). These mispairs can potentially lead to G to A transitions and G to C transversions, which have been observed in LuP-treated rats, 16 although they are considered as minor mutations relative to the three major mutations noted earlier.…”

“…Madder root has also been used as an herbal medicine for treating kidney and bladder stones , and urinary disorders . In Japan and Korea, madder color had been used as a natural food colorant and additive, and such use was banned in 2004 in both countries due to its toxicity in experimental animals. − In rats, madder root exerts carcinogenicity; , however, in humans madder root is classified as Group 3 (i.e., not classifiable as to its carcinogenicity to humans) by the International Agency for Research on Cancer . The reason for the low carcinogenic risk of lucidin in humans remains unclear.…”

Site‐Specific N2‐dG DNA Adducts: Formation, Synthesis, and TLS Polymerase‐Mediated Bypass

“…[ 79 ] Such miscoding events may lead to the G to C transversions as well as G to A transitions. [ 98 ] Mass spectral analyses was carried out to gain more details on the frameshift generation by hpol κ‐mediated TLS across LdG adduct. [ 99 ] These studies revealed error‐free TLS past LdG by hpol κ at physiological concentrations of dNTPs.…”