Normal DNA replication is stringently regulated to ensure a timely occurrence no more than once per cell cycle. Abrogation of the exquisite control mechanisms that maintain this process results in detrimental gains and losses of genomic DNA commonly seen in cancer and developmental defects. Replication initiation proteins, known as prereplicative complex (pre-RC) proteins, serve as a primary level of regulation, controlling when DNA replication can begin. Unsurprisingly, several pre-RC proteins are overexpressed in cancer and serve as good tumor markers. However, their direct correlation with increasing tumor grade and poor prognosis has posed a long-standing question: Are pre-RC proteins oncogenic? Recently, a growing body of data indicates that deregulation of individual pre-RC proteins, either by overexpression or functional deficiency in several organismal models, results in significant and consistently perturbed cell cycle regulation, genomic instability, and, potentially, tumorigenesis. In this review, we examine this broad range of evidence suggesting that pre-RC proteins play roles during oncogenesis that are more than simply indicative of proliferation, supporting the notion that pre-RC proteins may potentially have significant diagnostic and therapeutic value.

Two synthetic N-nitrosamines (N-3-methylbutyl-N-1-methyl acetonylnitrosamine and N-methyl-N-benzylnitrosamine), previously isolated from corn-bread which had been inoculated with moulds occurring in Linshien county, Northern China and subsequent nitrosation by sodium nitrite, were tested in Salmonella typhimurium strains TA1535 and TA100 in the presence of a liver postmitochondrial supernatant from Aroclor-treated rats. A concentration-dependent increase in the number of mutant colonies in both bacterial strains was observed when N-3-methylbutyl-N-1-methylacetonyl-nitrosamine was assayed in liquid suspension and N-methyl-N-benzylnitrosamine in plate incorporation assays. Our finding that mutagenic N-nitrosamines are present in foodstuffs that may be consumed in Linshien county are discussed in relation to the possible etiological role of these compounds in cancer of the oesophagus in that area.

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