Sensitivity to chromosomal breakage as risk factor in young adults with oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) may develop in young adults. In contrast to older patients, the well-known etiological factors, exposure to tobacco and alcohol, play a minor role in the carcinogenesis in this patient group. It has been suggested that an intrinsic susceptibility to environmental genotoxic exposures plays a role in the development of OSCC in these patients. The hypothesis was tested whether young OSCC patients have an increased sensitivity to induced chromosomal damage. SUBJECTS AND METHODS: Fourteen OSCC patients with an average age of 32 years (range 20-42) were selected. Peripheral blood lymphocytes and skin fibroblasts of patients and 14 healthy controls were subjected to the chromosome breakage test with Mitomycin C. This test is routinely used to identify Fanconi anemia patients, who are well-known for their inherited high sensitivity to this type of DNA damage, but also for the high risk to develop OSCC. Human papilloma virus status of the carcinomas was also determined. RESULTS: None of the 14 young patients with OSCC had an increased response in the MMC-chromosomal breakage test. All tumors tested negative for human papilloma virus. CONCLUSION: No evidence was obtained for the existence of a constitutional hypersensitivity to DNA chromosomal damage as a potential risk factor for OSCC in young adults.

Methods for Controlled Protein Depletion to Study Protein Function during Meiosis.

Proteins with potential roles in meiotic recombination often have essential or important functions during the mitotic cell cycle. In addition, proteins may have different functions at different times during meiosis. In such cases, it can be challenging to precisely determine protein function during meiosis using null or hypomorphic mutants. One example is the Sgs1-Top3-Rmi1 helicase-decatenase complex, which is required for normal vegetative growth and genome stability. In such cases, conditional loss-of-function mutants can be useful. In this chapter, we describe the construction of two types of conditional mutants, meiotic depletion alleles and auxin-induced degradation alleles, that allow protein depletion specifically during budding yeast meiosis, and illustrate their use with Sgs1. We also describe a modified method for the isolation of meiotic recombination intermediates that combines previous psoralen cross-linking and cetyltrimethylammonium bromide isolation methods.