Pharmacological coal tar induces G:C to T:A transversion mutations in the skin of muta mouse

Coal tar is a by-product of the distillation of coal. It consists of a complex chemical mixture of aromatic and aliphatic hydrocabons, with high concentrations of polycyclic aromatic hydrocarbons such as benzo[a]pyrene. We have previously shown that single painting on skin of mice increases the mutation frequency 16 times in murine epidermis cells (Thein et al. 2000). Here, we have determined the mutations by DNA sequencing. Coal tar was found to primarily induce G:C to T:A transversions and one-base pair deletions of G:C base pairs. More than half of the mutations were at CpG sites. The mutational spectrum is in agreement with that of benzo[a]pyrene and other polycyclic aromatic hydrocarbon mixtures.     

Detection of somatic changes in human cancer DNA by DNA fingerprint analysis

Minisatellite DNA probes which can detect a large number of autosomal loci dispersed throughout the human genome were used to examine the constitutional and tumour DNA of 35 patients with a variety of cancers of which eight were of gastrointestinal origin. Somatic changes were seen in the tumour DNA in ten of the 35 cases. The changes included alterations in the relative intensities of hybridising DNA fragments, and, in three cases of cancers of gastrointestinal origin, the appearance of novel minisatellite fragments not seen in the corresponding constitutional DNA. The results of this preliminary study suggests that DNA fingerprint analysis provides a useful technique for identifying somatic changes in cancers.     

Prognosis of hepatitis C virus-infected Canadian post-transfusion compensation claimant cohort

Summary.  Accurate prognostic estimates were required to ensure the sufficiency of the $1.1 billion compensation fund established in 1998 to compensate Canadians who acquired hepatitis C virus (HCV) infection through blood transfusion between 1986 and 1990. This article reports the application of Markov modelling and epidemiological methods to estimate the prognosis of individuals who have claimed compensation. Clinical characteristics of the claimant cohort ( n  = 5004) were used to define the starting distribution. Annual stage-specific transition probabilities (F0→F1, . . ., F3→F4) were derived from the claimants, using the Markov maximum likelihood estimation method. HCV treatment efficacy was derived from the literature and practice patterns were estimated from a national survey. The estimated stage-specific transition probabilities of the cohort between F0→F1, F1→F2, F2→F3 and F3→F4 were 0.032, 0.137, 0.150 and 0.097 respectively. At 20 years after the index transfusion, approximately 10% of all living claimants ( n  = 3773) had cirrhosis and 0.5% developed hepatocellular carcinoma (HCC). For nonhaemophilic patients, the predicted 20-year (2030) risk of HCV-related cirrhosis was 23%, and the risk of HCC and liver-related death was 7% and 11% respectively. Haemophilic patients who are younger and are frequently co-infected with human immunodeficiency virus would have higher 20-year risks of cirrhosis (37%), HCC (12%) and liver-related death (19%). Our results indicate that rates of progression to advanced liver disease in post-transfusion cohorts may be lower than previously reported. The Canadian post-transfusion cohort offers new and relevant prognostic information for post-transfusion HCV patients in Canada and is an invaluable resource to study the natural history and resource utilization of HCV-infected individuals in future studies.     

Peripheral arterial occlusive disease: P-31 MR spectroscopy of calf muscle

The effect of a graded exercise protocol on phosphorus-31 magnetic resonance (MR) spectroscopy of calf skeletal muscle in nine healthy (control) subjects and 16 patients with symptomatic peripheral arterial occlusive disease (PAOD) was assessed. Ankle-brachial pressure indexes were obtained in all 16 patients, and 10 patients underwent peripheral arteriography. Temporal profiles of pH and the inorganic phosphorus (Pi) index were calculated from the spectra. A Pi-index recovery rate constant was calculated for each subject. Arteriograms were graded by calculating the runoff resistance in the limb of interest. The pH profiles during exercise did not differ significantly between the PAOD patients and control subjects. The Pi-index recovery rate constant in the PAOD patients was significantly (P less than .01) smaller than in the control subjects. There was no significant correlation between recovery rate and the ankle-brachial pressure indexes, but there was a strong negative correlation between recovery rates and angiographic resistance grades, with smaller recovery rate constants in patients with increased arterial resistance. It is concluded that P-31 MR spectroscopy shows promise as a direct measure of tissue perfusion.