Naked DNA Raises Cancer Fears for Researchers

PHYLLIDA BROWN

FRESH evidence has emerged that laboratory workers who handle DNA without

taking precautions may be at risk of cancer. This has prompted the British

government to tighten its safety guidelines.

Research funded by the Health and Safety Executive has found that a

sequence of naked human DNA can cause tumours when applied directly to the

broken skin of mice. David Bosworth, a specialist inspector in molecular

biology for the HSE, said the decision to fund research into genes which

trigger cancer had been prompted by an unexplained cluster of rare cancers

among scientists at the Pasteur Institute in Paris (This Week, 17 February).

A team of laboratories of the Cancer Research Campaign in Glasgow say

their work is the first they know of to show that a sequence of naked DNA

from human cancer cells can trigger the development of tumours in living

animals. The sequence was that of a human oncogene a gene that can mutate

into a form capable of turning healthy cells malignant. Other researchers

have induced tumours in chickens and mice by inoculating them with an oncogene

from a chicken virus.

Scientists stress that handling oncogenes is much less risky than work

with disease-causing organisms such as HIV. But researchers at a seminar

organised by their union, MSF, said last week that they lacked adequate

training in safe practice.

The team in Glasgow applied the pure DNA sequence of a cloned, mutated

oncogene from the group of ras genes to the backs of the mice. Within weeks

the animals developed dark patches on their backs, and after several months

they developed tumours of endothelial cells lining the blood vessels and

lymph vessels.

A single line of cells taken from the tumours and cultured in the laboratory

was found to contain the human ras gene, says the team. When the researchers

injected the cultured cells into different mice, these animals also developed

tumours. The work has been submitted to the journal Oncogene for publication.

The Health and Safety Commission informed the 380 laboratories in Britain

that handle oncogenes when it learned of the researchers preliminary findings

last year. The commissions Advisory Committee on Genetic Modification has

now revised its guidelines and these will be available shortly. The commission

is also doubling the number of its specialist inspectors to eight because

of pressure of work.

The findings . . . led us to reexamine our guidance, said Tony Taylor,

the secretary to the ACGM. Bosworth said the research had not proved the

existence of a risk to people, but the executive wanted to act before such

a risk were proven.

Taylor said there was a need for more research to find out whether oncogenes

can also trigger tumours when inhaled or swallowed, although he said scientists

felt that either possibility was very unlikely. The gut digests foreign

DNA regularly and enzymes in the lining of the lung should break it down

if it is inhaled.

The existing Guidance Note 1 for handling of oncogenes, drawn up by

the ACGM in 1984, advises workers to wear gloves and avoid using sharp instruments,

and specifies when work should be done in a fume cupboard or safety cabinet.

The new note includes procedures for cleaning up after a spill of DNA, and

says workers with broken skin on their hands or forearms should seek medical

advice before handling oncogenes.

Britains guidance note on oncogenes is not legally binding, but last

years legislation on the Control of Substances Hazardous to Health makes

laboratories responsible for assessing risk, maintaining equipment and training

staff in safety. An EC directive on genetically modified organisms, which

broadly covers the field, will be implemented by October 1991.

Robin Weiss, director of the Chester Beatty Laboratories of the Institute

of Cancer Research in London, believes Britains guidance is adequate as

it stands but says some scientists may be cavalier in the way they handle

DNA. I think putting the regulations into practice should be tightened,

he told New Scientist.