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J Wakhisi

Publications and source records attributed to J Wakhisi.

10 recordsLinked to original sources
PubMed2001

Lessons learned from colorectal model of tumourigenesis.

Genetic analytical techniques were carried out to identify mutations in adenomatous polyposis coli (APC) gene and K-ras oncogene in colorectal tumourigenesis. These two genes are said to be early mutation genes among other mutation genes that constitute the model for colorectal tumourigenesis. To do this analysis, DNA was isolated from colorectal formalin fixed paraffin-embedded tumour tissue sections. The sections were deparaffinised, digested in proteinase-K, followed by DNA isolation. The DNA was amplified by Polymerase Chain Reaction (PCR), screened by using Denaturing Gradient Gel Electrophoresis (DGGE) or Single Strand Conformation Polymorphism (SSCP) and then sequenced. These results lend support to the fact that colorectal cancer and indeed cancer in general develops through a multi-step process; also that accumulation of genetic mutations underlie the development of neoplasia. We are in the process of extending this study to cancer of oesophagus to see if a similar or parallel model of carcinogenesis holds and in what sequence it is.

Adenomatous Polyposis Coli↗
PubMed1993

The impact of vitamins A,C,E, and selenium compound on prevention of liver cancer in rats.

A study was initiated to determine the impact of vitamins A, C, E, and selenium compound (Se) on the prevention of liver cancer. Sixty animals were fed a diet with or without these vitamins followed by aflatoxin B treatment for a period of 24 months. Most of the animals fed a diet devoid of vitamins developed liver cancer, while none or only a few of the animals given vitamins suffered during this period. We suggest that vitamins can inhibit liver cancer by inducing hepatic microsomal enzymes that metabolise aflatoxins to noncarcinogenic products.

Aflatoxin B1↗
PubMed1989

Inhibition of AFB1-induced liver cancer and induction of increased microsomal enzyme activity by dietary constituents.

A long-term study, using male Wistar rats, was initiated to determine whether the effects of dietary constituents on AFB1-induced liver cancer could be associated with altered microsomal enzyme activity. They were maintained on mice pellets mixed with specific dietary constituents for 7 days and then given a single carcinogenic dose of AFB1 (500 micrograms/rat). After three months, the dietary constituents were discontinued and the animals were left on mice pellets and drinking water only for a period of about 20 months. At the end of the trial period, it was observed that dietary mixtures containing small quantities of either beta-carotene, ascorbic acid, GSH, vitamin E, selenium salt, or uric acid, effectively inhibited the development of AFB1-induced liver cancer and induced increased microsomal enzyme activity. Whereas beta-carotene and uric acid were the most effective inhibitors, vitamin E was the least, yet a significant inhibitor of liver cancer. Hepatic levels of cytochrome P-450, aniline hydroxylase and chlorpromazine demethylase were significantly induced in rats fed fortified food followed by AFB1 treatment than in control animals. The inhibition of liver cancer by dietary factors was probably due to their ability to induce the activity of hepatic microsomal enzymes. Increased enzyme activity could lead to rapid activation of AFB1 metabolism, resulting in loss of activated AFB1 metabolites that attack cell components. Inhibition of liver cancer is therefore associated with induction of increased microsomal enzyme activity.

Aflatoxins↗
PubMed1988

Detection of exposure to aflatoxin in an African population.

Urinary excretion of 8,9-dihydro-8-(7'-guanyl)-9-hydroxyaflatoxin (AFB-Gua) was studied in areas of different liver cancer incidence in Kenya. Of 983 urine samples analysed for AFB-Gua by high-performance liquid chromatography, 12.6% gave positive results. The chemical identity of AFB-Gua was verified by synchronous scanning fluorescence spectrophotometry. A moderate degree of correlation between prevalence of exposure to aflatoxin B1 and liver cancer incidence could be established in Bantu. People living in areas with high exposure to aflatoxin B, form antibodies that recognize an aflatoxin B1 epitope.

Aflatoxin B1↗
PubMed1987

Aflatoxin exposure measured by urinary excretion of aflatoxin B1-guanine adduct and hepatitis B virus infection in areas with different liver cancer incidence in Kenya.

Two major etiological agents, hepatitis B virus and aflatoxin B1, are considered to be involved in the induction of liver cancer in Africa. In order to elucidate any synergistic effect of these two agents we conducted a study in various parts of Kenya with different liver cancer incidence in order to establish the rate of exposure to aflatoxin and the prevalence of hepatitis infections. Of all tested individuals 12.6% were positive for aflatoxin exposure as indicated by the urinary excretion of aflatoxin B1-guanine. Assuming no annual and seasonal variation, a regional variation in the exposure was observed. The highest rate of aflatoxin exposure was found in the Western Highlands and Central Province. The incidence of hepatitis infection nationwide as measured by the presence of the surface antigens was 10.6%, but a wide regional variation was observed. A multiplicative and additive regression analysis to investigate if hepatitis and aflatoxin exposure had a synergetic effect in the induction of liver cancer was negative. However, a moderate degree of correlation between the exposure to aflatoxin and liver cancer was observed when the study was limited to certain ethnic groups. The study gives additional support to the hypothesis that aflatoxin is a human liver carcinogen.

Aflatoxin B1↗
PubMed1985

Detection of 8,9-dihydro-(7'-guanyl)-9-hydroxyaflatoxin B1 in human urine.

A possible role of aflatoxin B1 (AFB) in the etiology of human liver cancer has been suggested from several epidemiological studies. This has been based upon the association between consumption of AFB-contaminated food and the liver cancer incidence in different parts of the world. To further establish the role of AFB as a major factor, we initiated a pilot study in three different districts of Kenya to determine the number of individuals exposed to significant amounts of AFB as measured by the urinary excretion of 8,9-dihydro-8-(7-guanyl)-9-hydroxyaflatoxin B1 (AFB-Gua), an adduct formed between the ultimate carcinogenic form of AFB and nucleic acids. This product has previously been detected in urine from rats treated with AFB. Urine collected at the outpatient clinics at the district hospitals were concentrated on C18 Sep-Pak columns and analyzed by high-pressure liquid chromatography under two different chromatographic conditions. The chemical identity of the samples showing a positive response in both chromatographic systems was verified by synchronous scanning fluorescence spectrophotometry. The highest number of individuals with detectable urinary AFB-Gua lived in either Murang'a district or the neighboring Meru and Embu districts. In Murang'a district a rate of 12% was observed in the January-March period, while only 1 of 32 patients (3%) had a detectable exposure in July-August.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Detection of putative adduct with fluorescence characteristics identical to 2,3-dihydro-2-(7'-guanyl)-3-hydroxyaflatoxin B1 in human urine collected in Murang'a district, Kenya.

Food samples collected in Murang'a district, Kenya are known to be contaminated with a mycotoxin, aflatoxin B1 (AFB), and a positive correlation exists between the dietary intake of AFB and the incidence of liver cancer. When urine samples collected in this district were analyzed for the presence of 2,3-dihydro-2-(7'-guanyl)-3-hydroxyaflatoxin B1 (AFB-GuaI) by h.p.l.c., 6 of 81 samples had a detectable level of a compound whose fluorescence spectrum was identical to chemically synthesized AFB-GuaI as confirmed by photoncounting fluorescence spectrophotometry. These results are an indication of interaction between the ultimate carcinogenic form of AFB and cellular nucleic acids in vivo and further support the hypothesis that AFB may play an important role in the etiology of human liver cancer.

Aflatoxin B1↗
PubMedDate not supplied

Evidence for human antibodies that recognize an aflatoxin epitope in groups with high and low exposure to aflatoxins.

Antibody activity against an aflatoxin epitope has been detected in serum from individuals who live in Kenya and who experience high exposure to aflatoxin B1. The activity was higher than in Danish people. The highest antibody activity was found in individuals who were recently exposed to aflatoxin B1. The ratio between IgG and IgM activities was higher in individuals with a high antibody titer. The specificity of the antibody activity differed in the serums obtained from Danish and Kenyan persons ("Danish" and "Kenyan" serum, respectively). The activity in Danish serum was inhibited by an aflatoxin-like substance isolated from human urine, whereas aflatoxin B1 did not inhibit the activity. In contrast, the activity in Kenyan serum was not inhibited by the aflatoxin-like substances. Therefore, the presence of antibodies against aflatoxin in humans indicates exposure to aflatoxin or aflatoxin-antigenic material. However, the biological consequences of these antibodies remain unknown.

Aflatoxin B1↗