Familial adenomatous polyposis in two Black South African families.

The apparent low incidence of colon cancer in the Black population of South Africa has been ascribed to a non-Western diet. The present authors report the identification of two common 5-bp deletions at codons 1309 and 1061 of the adenomatous polyposis coli (APC) gene in a Xhosa and Zulu patient, respectively. The in vitro transcription/translation test (PTT) and a non-radioactive heteroduplex method, which facilitates resolution of enzymatically amplified DNA by agarose gel electrophoresis, were used for mutation detection. This study represents the first report of APC mutations in indigenous Black individuals clinically diagnosed with familial adenomatous polyposis coli (FAP). The two deletion mutations are responsible for FAP in 35% of affected South Africans, a frequency similar to that described in several other non-African populations. The apparently low incidence of colon cancer in the African population may be ascribed either to the rare occurrence of the 'second hit' needed for polyp formation or to a lower incidence of mutations in the APC gene.

Differential cytotoxicity of trace metals in cisplatin-sensitive and -resistant human ovarian cancer cells.

Cellular resistance of cisplatin is related to various factors such as membrane transformations, changes in cellular transport systems, and an increased efflux of cisplatin by the tumor cells. Deficiencies of one or more trace metals can affect normal physiological functions, leading to altered enzymatic activities and a reduction in immune responses. This in vitro investigation was undertaken to study and determine the differential cytotoxicity of certain trace metals in human ovarian cancer cells that were sensitive and resistant to cisplatin. Standard cytotoxicity assays were performed using the neutral red assay. In general, the cisplatin-resistant cells exhibited an increased resistance to the externally supplied trace metals. For both cell lines the rank order of cytotoxicity from greatest to least with the non-essential metals was Cd2+ > Bi3+, and for the macrometals, Ca2+ > K+ > Mg2+. The transition metals and selenium exhibited a slight difference between the two cell lines with respect to the order of cytotoxicity. The cisplatin-sensitive cells had a rank order of V5+ > Se6+ > Cu2+ > Zn2+ > Fe3+, from greatest to least toxicity. The cisplatin-resistant cells had a rank order of Cu2+ > V5+ > Se6+ > Zn2+ > Fe3+. Since trace metals have various functions in maintaining normal health, these results provide key baseline cytotoxicity data and show that, in general, cytotoxic resistance to the trace metals tested followed a pattern similar to cellular cisplatin resistance.

The cytotoxic interaction of inorganic trace elements with EDTA and cisplatin in sensitive and resistant human ovarian cancer cells.

Cisplatin (CDDP)-sensitive and -resistant human ovarian cells were studied in vitro with the objective of enhancing CDDP cytotoxicity by the addition of a metal and the chelate ethylenediaminetetraacetic acid (EDTA), to the CDDP. Chelateable elements, such as bismuth, calcium, cadmium, copper, iron, magnesium, selenium, vanadium, and zinc, when added to CDDP and in the presence of EDTA increased the cytotoxicity of the CDDP as compared to CDDP treatment alone.

The hand-foot-uterus syndrome: a case study.

An autosomal dominant syndrome is described in 26 members of six generations in a single family. Distal extremity malformations are characteristic and superficially resemble those of arthrogryposis, chondroectodermal dysplasia, Cornelia de Lange syndrome, Faconi's anemia or Holt-Oram syndrome. There is an absence of spinal deformity, and females of the disorder have duplication of the genital tract.