Exposure of iron-loaded C57BL/10ScSn mice to the polychlorinated biphenyls (PCBs) mixture Aroclor 1254 in the diet (0.01%) for 5 weeks caused massive hepatic porphyria far greater than occurred with PCBs alone. This regime eventually causes hepatocellular carcinoma. Hepatic microsomal ethoxy-, pentoxy-, and benzyloxyresorufin dealkylase activities (respectively EROD, PROD, and BROD) catalyzed primarily by cytochrome P4501A1 and 2B isoenzymes were markedly induced after 2 weeks of diet (when no porphyria had developed) but showed little effect of iron. EROD activity in the nuclear membrane was also induced by the PCBs as was CYP1A1 protein when shown by immunoblotting. Nuclear dealkylase activities of PCBs-treated mice were considerably less than microsomal activities but were stimulated by iron pretreatment. The mechanism of the iron-enhanced toxicity may be due to oxidative damage associated with chronic induction of CYP1A1 isoforms. Lucigenin-enhanced chemiluminescence (CL) by microsomes and nuclear membranes was used as a method to estimate their potential to form reactive oxygen species. Despite CL being induced by PCBs it was less with microsomes from iron-treated mice. In a comparison of a variety of inducers of microsomal cytochrome P450 there was no correlation between inducer, uroporphyrogenic agent, and intensity of CL. On the other hand, cytosolic glutathione S-transferase (GST) activities with 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene (DCNB) as substrates, were also induced by the PCBs mixture, the induction with DCNB being synergistically potentiated by iron pretreatment. Complementary results were observed by immunocytochemistry using anti alpha-GST antibody. In contrast, total glutathione peroxidase activity and selenium-dependent glutathione peroxidase activity were depressed by PCBs but particularly in mice also administered iron. The results illustrate that PCBs not only induce CYP1A1 in microsomes but also in the nuclear membrane, which may be of significance in the mechanism of the iron-enhanced carcinogenicity of these chemicals. The iron-enhanced induction of GST with accompanying depletion of glutathione peroxidase provides evidence for oxidative processes induced in vivo by the PCBs.

THERE IS CURRENTLY A LOT OF DISCUSSION about how to value financial instruments in companies' and – specifically in this context – banks' financial statements. Some advocate a move to full fair-value accounting; others promote so-called 'dynamic provisioning'. An article in the June 2000 Review set out some of the issues in relation to the former 2 ; this article looks at the latter. It first describes current practice with regard to bank loan provisioning and outlines how dynamic provisioning might work. It goes on to discuss the issues that would be involved in implementing dynamic provisioning, illustrating them with an example of a simple loan portfolio. These issues include how expectations of future losses might be set and whether dynamic provisioning could be used to smooth profits between accounting periods. Bank lending and the current approach to bank provisioning Under historic cost accounting, provisions are made for losses recognised at the balance sheet date. In relation to specific provisions, the UK Statement of Recommended Accounting Practice (SORP) on Advances 3 states that: " A loan is impaired when, based on current information and events, the bank considers that the creditworthiness of a borrower has undergone a deterioration such that it no longer expects to recover the advance in full ". Regarding general provisions, the SORP says that: " Experience shows that portfolios of advances often contain advances which are in fact impaired at the balance sheet date, but which will not be specifically identified as such until some time in the future…To cover the impaired advances which will only be identified as such in the future, a general provision should be made ". The distinction between the two is largely one of practical implementation: in both cases provisions are made only in respect of impairment believed to exist at the balance sheet date. The approach under US and international accounting standards is similar (Box 1). This accounting approach is rather different from the one implicit in banks' approach to lending. Banks expect that a proportion of their loan portfolios will be lost each year, as some borrowers will not be able to repay the loans. These are 'expected losses' , but actual losses may clearly be different from what a bank expects ex ante. Such unexpected losses could arise, for example, because of an unusually severe economic downturn. When calculating the unexpected loss, banks increasingly think in terms of …