Effect of partial hepatectomy on the response of rat liver to aflatoxin B1.

The effect of partial hepatectomy (PH) on aflatoxin B1 (AFB1) action in rat liver has been examined using adult male Fischer 344 rats. The elevated levels of hepatic DNA synthesis, present 26 hr after PH (> 15 times the control level) and 33 hr after PH, are rapidly inhibited by i.p. administration of AFB1. The percentage inhibitions are greater than those observed using intact or sham-operated animals. However, it was possible to demonstrate elevation of DNA synthesis in PH rats treated with AFB1. Rats 2 hr after being treated with AFB1 (0.075 mg/kg) at 24 and 31 hr after PH exhibited levels of DNA synthesis 380 to 400% of those present in sham-operated uninjected controls. After 62 weeks, the livers of the PH rats treated with AFB1 displayed no hepatocellular carcinoma. There was present, however, an increased incidence of lesions believed to be preneoplastic. The differences between the long-term effects of AFB1 and other hepatocarcinogens on the livers of PH rats are discussed in terms of their relative capacities and modes of action in inhibiting DNA synthesis.

[1]  G. Neal,et al.  The formation of 2,3‐dihydro‐2,3‐dihydroxy aflatoxin B1 by the metabolism of aflatoxin B1 in vitro by rat liver microsomes , 1979, FEBS letters.

[2]  G. Neal,et al.  The analysis of aflatoxins by high-performance liquid chromatography. , 1979, Analytical biochemistry.

[3]  G. Neal,et al.  Some high-performance liquid-chromatographic studies of the metabolism of aflatoxins by rat liver microsomal preparations. , 1978, The Biochemical journal.

[4]  D. Judah,et al.  Development of resistance to cytotoxicity during aflatoxin carcinogenesis , 1977, Nature.

[5]  D. Judah,et al.  The effects of prolonged feeding with aflatoxin B1 on adult rat liver. , 1976, Cancer research.

[6]  G. Neal,et al.  Some studies of the effects of aflatoxin B1 in vivo and in vitro on nucleic acid synthesis in rat and mouse. , 1976, Chemico-biological interactions.

[7]  T. Campbell,et al.  The role of aflatoxin metabolism in its toxic lesion. , 1976, Toxicology and applied pharmacology.

[8]  R. Squire,et al.  Report of a workshop on classification of specific hepatocellular lesions in rats. , 1975, Cancer research.

[9]  V. Craddock.  Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine, diethylnitrosamine and methyl methanesulphonate, on liver regenerating after partial hepatectomy. II. Alkylation of DNA and inhibition of DNA replication. , 1975, Chemico-biological interactions.

[10]  N. Bucher,et al.  Regeneration of liver in rats in the absence of portal splanchnic organs and a portal blood supply. , 1973, Cancer research.

[11]  G. Neal.  Inhibition of rat liver RNA synthesis by aflatoxin B. , 1973, Nature.

[12]  V. Craddock.  Liver carcinomas induced in rats by single administration of dimethylnitrosamine after partial hepatectomy. , 1971, Journal of the National Cancer Institute.

[13]  S. Sternberg,et al.  7,12-dimethylbenz(a)anthracene and hepatic neoplasia in regenerating rat liver. , 1970, Chemico-biological interactions.

[14]  H. Stich,et al.  Chromosomes of tumor cells. II. Effect of various liver carcinogens on mitosis of hepatic cells. , 1961, Journal of the National Cancer Institute.