Ch4.0&4.1 Flashcards

1
Q

What initial theory did cancer biologists develop about tumor viruses in the 1970s?

A

Tumor viruses might infect susceptible tissues and transform cells, leading to the formation of large cell masses that become tumors.

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2
Q

How did the initial tumor virus theory become challenged?

A

Most human cancers did not spread like infectious diseases, significant cancer clusters were rare, and attempts to isolate viruses from tumors were mostly unsuccessful.

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3
Q

How many human tumor types could be clearly linked to viral agents?

A

Only two commonly occurring tumor types in the Western world - cervical carcinomas and hepatomas (liver carcinomas) - could be clearly tied to specific viral agents.

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4
Q

What were the two main responses to the failure of the tumor virus theory?

A

Some researchers argued that chemical and physical carcinogens activated latent viruses, while others began investigating cellular genomes as a source of cancer-causing genes.

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5
Q

Who pioneered early research on chemical cancer induction?

A

Katsusaburo Yamagiwa, who demonstrated in the early 20th century that repeated application of coal tars on rabbit ears could induce skin carcinomas.

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6
Q

What early evidence existed about non-viral cancer causes?

A

A PhD thesis in Paris documented over 100 human cancer cases, largely of the skin, in individuals who worked with X-ray tubes.

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7
Q

What unique characteristic do retroviruses have regarding genome integration?

A

Retrovirus genomes can become integrated into germ-line chromosomes and be transmitted as Mendelian alleles across generations.

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8
Q

How can endogenous proviruses be activated?

A

In some cases, they can be activated by specific conditions, such as culturing mouse fibroblasts with bromodeoxyuridine (BrdU).

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9
Q

What hypothetical mechanism did some researchers propose for human cancer formation?

A

They suggested that mutagenic carcinogens might activate latent endogenous retroviruses, which could then spread and cause cancer.

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10
Q

What percentage of the human genome derives from endogenous retroviral genomes?

A

Approximately 8% of the human genome comes from endogenous retroviral genomes.

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11
Q

How many retrovirus-derived segments in the human genome might be genetically intact?

A

Only several of the approximately 40,000 retrovirus-derived segments have been shown to be potentially capable of specifying infectious virus particles.

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12
Q

What is unique about the HERV-K virus subfamily?

A

It has entered the human germ line relatively recently, and several of its proviruses appear intact, though they have not been found to produce infectious viruses.

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13
Q

When did the ancient germ-line retroviral infections occur?

A

The infections occurred 5 million years ago and earlier in ancestral primates.

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14
Q

Why did the endogenous retrovirus cancer causation models collapse?

A

Supportive evidence was not forthcoming, and infectious retroviral particles could not be verified in human tumors.

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15
Q

What happened to most endogenous retroviral genomes in human evolution?

A

They progressively mutated into sequences no longer capable of specifying infectious retrovirus particles and became part of junk DNA.

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16
Q

How did tumor virus research ultimately contribute to cancer understanding?

A

It helped uncover cellular cancer-causing genes (oncogenes and tumor suppressor genes) despite failing to prove viruses cause all cancers.

17
Q

What alternative source of cancer-causing genes did researchers begin to explore?

A

Researchers started investigating the cellular genome with its tens of thousands of genes.

18
Q

By when was the cell genome recognized as a source of cancer-driving genes?

A

By the late 1980s, the cell genome was recognized as a rich source of genes driving human cancer cell proliferation.

19
Q

What made the initial tumor virus theory attractive?

A

Tumor viruses could transform normal rodent and chicken cells into tumor cells using only a small number of introduced genes.

20
Q

How did researchers explain the lack of horizontal cancer transmission?

A

They proposed that endogenous viruses might spread within an individual’s body but not between individuals.

21
Q

What technological evidence complicated the virus cancer theory?

A

Reverse transcriptase-containing virus particles were difficult to find in human tumors.

22
Q

Why did the human germ line stop acquiring new functional endogenous proviruses?

A

The reason remains unclear, though it is noted that other mammalian species continue to acquire such proviruses.

23
Q

What early evidence suggested non-viral cancer causes?

A

Research showed that chemical agents and radiation could induce cancers in laboratory animals and humans.

24
Q

How did the perspective on cancer causation evolve?

A

From viewing viruses as the key agents triggering all human cancers to recognizing cellular genetic mechanisms.

25
Q

What made the endogenous retrovirus activation hypothesis appealing?

A

It offered a potential explanation for cancer formation in the absence of direct viral infection.

26
Q

What significant realization emerged about human endogenous retroviruses?

A

Most are ancient genetic relics that have lost their ability to produce infectious particles.

27
Q

What specific publication helped challenge the viral cancer theory?

A

A PhD thesis in Paris documenting over 100 human cancer cases from X-ray tube exposure.

28
Q

How did researchers respond to the failure of the virus cancer theory?

A

They shifted focus to investigating the cellular genome as a potential source of cancer-causing genes.

29
Q

What was ironic about tumor virus research?

A

Despite failing to prove viruses cause all cancers, it was crucial in uncovering cellular cancer-causing genes.