Chemical Probes and Possible Targets for the Induction of Aneuploidy

Liang, Jan C.; Brinkley, B. R.

doi:10.1007/978-1-4613-2127-9_33

Cited by 37 publications

(7 citation statements)

References 47 publications

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“…Nocodazole disrupts meiosis in a similar manner to the other spindle poisons, colchicine and vinblastin, which interfere with the assembly of the spindle microtubules by inhibiting the polymerization of tubulins (Liang & Brinkley, 1985). It was not unexpected, therefore, that the dose response of the oocytes to the application of nocodazole showed a similar profile to that reported for vinblastine sulphate in vivo (Russo & Pachierotti, 1988).…”

Section: (I) Nocodazole As An Efficient Inducer Of Nondisjunctionmentioning

confidence: 60%

Pattern and frequency of nocodazole induced meiotic nondisjunction in oocytes of mice carrying the ‘tobacco mouse’ metacentric Rb(16.17)7Bnr

Everett¹,

Searle²

1995

Genet. Res.

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Oocytes from (C3H/HeH x l O l /^F j and Rb(16.17)7Bnr homozygous females were exposed to a range of doses of nocodazole in vitro. The spindle poison caused a dose dependent increase in metaphase I (MI) arrest and hyperploidy. A concentration of 003 /*g/ml was found to induce a maximum hyperploid frequency of 31 % and 11-6% respectively without a high level of MI arrest. Between 0-03 and 005/tg/ml MI arrest increased substantially and reached a frequency of approximately 90%. In a further experiment oocytes from Rb7 homozygous, heterozygous and 3H1 females were exposed to 003 fig/vcA nocodazole 4, 6 or 8 h after the onset of maturation. The phase at which the spindle was inhibited resulted in a specific pattern of nondisjunction which in turn was dependent on whether the female carried an Rb metacentric. 3H1 oocytes gave a normally distributed pattern of increase in aneuploid frequency (over the spontaneous value) centering around a 6 h application. This was thought to be due to the interaction of chromosomes with the microtubules of the spindle during attachment and/or alignment. In contrast both Rb homozygotes and heterozygotes gave the same biphasic response, with a high frequency of aneuploidy in the oocytes when nocodazole was applied 4 and 8 h after the onset of maturation. In Rb homozygotes we demonstrated that the Rb bivalent underwent nondisjunction more frequently than the average acrocentric, when nocodazole was administered early. It can be assumed that the Rb trivalent in Rb heterozygotes showed a similar response. This early Rb specific effect, in combination with a delayed-version of the acrocentric effect found in the 3H1 mice was thought to generate the biphasic pattern. We discuss the implications of (a) the different meiotic behaviours of metacentrics and acrocentrics and (b) the meiotic delay in Rb mice.

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Section: (I) Nocodazole As An Efficient Inducer Of Nondisjunctionmentioning

confidence: 60%

Pattern and frequency of nocodazole induced meiotic nondisjunction in oocytes of mice carrying the ‘tobacco mouse’ metacentric Rb(16.17)7Bnr

Everett¹,

Searle²

1995

Genet. Res.

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“…This has already been demonstrated by us and others [Liang and Brinkley, 1985;Oenfelt, 1986;Oshimura and Barrett, 1986;Jensen et al, 1993;Parry et al, 1996;Li et al, 1997;Matsuoka et al, 1997;Duesberg et al, 2000]. For example, the lipophilic polycyclic hydrocarbons may disrupt microtubules by binding to tubulin proteins (compare the phenol method for protein extraction), and thus induce chromosome non-disjunction [Jensen et al, 1993;Li et al, 1997;Matsuoka et al, 1997].…”

Section: Stage One: Generation Of Aneuploidymentioning

confidence: 76%

“…Their data collectively show that probably all chemical carcinogens, both genotoxic and non-genotoxic ones, can function as aneugens or physically altering either the chromosomes or the spindle apparatus (see, above, Stage one: generation of aneuploidy) [Natarajan et al, 1984;Liang and Brinkley, 1985;Cimino et al, 1986;Galloway and Ivett, 1986;Jensen and Thilly, 1986;Oenfelt, 1986;Parry and Sors, 1993;Parry et al, 1996;Aardema et al, 1998;Duesberg et al, 2000].…”

Section: Carcinogens Cause Aneuploidymentioning

confidence: 99%

Aneuploidy, the somatic mutation that makes cancer a species of its own

Duesberg

Rasnick

2000

Cell Motil. Cytoskeleton

207

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“…47,48 Depending on the degree of aneuploidy, they range from 3% to almost 100% per cell generation. 30,36,38,40,41,49 These high rates of variation generate large constitutive cohorts of variants or subspecies, which allow rapid adaptations and phenotypic "progressions."…”

mentioning

confidence: 99%