Fanconi’s anaemia

LED, lowest effective dose HID, highest ineffective dose in-vitro tests, pg/nil, in-vivo tests, mg/kg bw/day inj, injection im, intramuscular po, oral ip, intraperitoneal inh, inhalation Fanconi s anaemia (homozygotes and heterozygotes)... 

Bimodal response, 24% positive, 76% negative no correlation to GSTMl deficiency Positive response correlates with GSTTl deficiency f Fanconi s anaemia (heterozygotes)... 

Fanconi s anaemia (homozygotes and heterozygotes), ataxia telangiectasia, xeroderma pigmentosum, normal... 

Auerbach, A.D. Wolman, S.R. (1976) Susceptibility of Fanconi s anaemia fibroblasts to chromosome damage by carcinogens. Nature, 261, 494-496... 

Strathdee CA, Gavish H, Shannon WR, Buchwald M. Cloning of cDNAs for Fanconi s anaemia by functional complementation. Nature 1992 356 763-767. 

Fanconi s anaemia (FA) is an autosomal disorder with bone marrow failure, variable presence of developmental abnormalities, hypersensitivity to DNA cross-linking agents, and a very high incidence of cancer. Different complementation groups have been cloned, but the exact pathway remains uncertain. However, data suggest that the syndrome is linked to mutations in XRCC9 and XRCCl 1 and therefore to defects in the homologous recombination repair pathway (summarized in [26]). 

Cells from patients with the genetic disease Fanconi s anaemia, show unusual sensitivity to the cytotoxic and clastogenic effects of difunctional alkylating agents. These cells are also unusually sensitive to cisplatin (72). Such sensitivity is not the result of decreased binding of platinum to DNA but it remains to be determined if repair of various lesions in these cells is abnormal. 

Pagano, G. and Youssoufian, H., Fanconi s anaemia proteins concurrent roles in cell protection... 

S. A. Latt, G. Stetten, L. A. Juergens, G. R. Buchanan, and P. S. Gerald, Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi s anaemia, Proc. Natl. Acad. Sci. IJ.S.A. 72, 4066-4070 (1975). 

Two further cases of hepatocellular carcinoma associated with anabolic steroid therapy have been reported. One was a child with Fanconi s anaemia, who was treated with anabolic steroids for 50 months (2 ). The other also occurred in a patient with Fanconi s anaemia following 4 years medication with androgenic, anabolic steroids (3 ). Examination of the livers of 2 patients with acquired aplastic anaemia who had been treated with similar compounds for 3 months prior to death revealed generalized parenchymal hyperplasia in one and widespread nodular hyperplasia in the other. Since 1971, 10 cases of hepatocellular carcinoma during medication with anabolic steroids have been reported in the literature. The prognosis is poor with a survival time of less than a year. The similar medical history indicates but does not prove a cause-effect relationship between disease and medication. The data must, however, be viewed alongside that pointing to hepatic tumours as complications of treatment with other types of steroids, notably the oral contraceptives. 

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