Date of Graduation

1997

Document Type

Dissertation/Thesis

Abstract

This work was conducted to determine the frequency and distribution of stable cytogenetic damage (translocations and insertions) in human lymphocytes using chromosome painting. Included were cells exposed to gamma radiation in vitro and selected individuals from a healthy unexposed California population (n = 27), and a population of Russians exposed during cleanup work the Chernobyl nuclear accident (n = 120) and Russian controls (n = 69). The in vitro results showed that the frequencies of radiation-induced stable aberrations in chromosomes 3, 5 and 6 were proportional to chromosome size. The results in the California population showed that the frequencies of spontaneous aberrations were proportional to chromosome size in chromosomes 1 through 6. Aberration frequencies measured in chromosomes 3, 5 and 6 as a set were highly correlated with those observed in chromosomes 1, 2 and 4 as a set after adjusting for the different amounts of the genome that were painted. In contrast, the distribution of stable aberrations in chromosomes 1, 2 and 4 in both radiation-exposed and control Russian populations were not proportional to chromosome size. Some subjects had a distribution of damage that was not proportional to chromosome size due to the presence of clones of abnormal cells, with approximately 1 in 20 subjects in all populations found to possess clones. Using Chi-square values determined from the observed and expected numbers of aberrations a simple statistical method is presented for identifying subjects that may possess clones. It was determined whether differences exist in the aberration frequencies measured by two scoring systems, the classical method where all exchanges are assumed to be reciprocal and PAINT, where no such assumptions are made. The two scoring systems were highly correlated in all populations for translocations and differed by a constant value (PAINT x {dollar}\\sim{dollar}0.60 = classical method). Approximately 30% of translocations were observed to be nonreciprocal due to lack of detection of exchanges involving small amounts of material, or to a telomere or nonreciprocal exchange mechanism. Variation between chromosomes in nonreciprocal translocation frequencies contributed to the nonproportional distribution seen in the Russian control population. The minimum detectable sizes of exchanged chromosome segments was calculated from the numbers of reciprocal and nonreciprocal translocations. While these detection values were similar to published values, there was considerable variation between chromosomes as well as sex differences which may also contribute to the nonproportional damage distributions.

Download

Share

COinS