Russia invaded Ukraine on Feb. 24, and shortly after, Russian President Vladimir Putin had obliquely raised the possibility of a nuclear strike. The conflict has also heightened concerns about the safety of Ukraine's nuclear plants.
U.N. Secretary General Antonio Guterres joined the thousands packed into the Peace Park in the center of the city to mark the anniversary of the bombing that killed 140,000 before the end of 1945, only the second time a U.N. Secretary-General has taken part in the annual ceremony.
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"Nuclear weapons are nonsense. They guarantee no safety - only death and destruction," Guterres said.
"Three quarters of a century later, we must ask what we've learned from the mushroom cloud that swelled above this city in 1945."
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Guterres sidestepped a direct citation of Russia, which calls its attack of Ukraine a "special military operation."
Hiroshima mayor Kazumi Matsui, whose city this year did not invite the Russian ambassador to the ceremony, was more pointed and critical of Moscow's military actions in Ukraine.
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"In invading Ukraine, the Russian leader, elected to protect the lives and property of his people, is using them as instruments of war, stealing the lives and livelihoods of civilians in a different country," Matsui said.
"Around the world, the notion that peace depends on nuclear deterrence gains momentum," Matsui added.
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"These errors betray humanity's determination, born of our experiences of war, to achieve a peaceful world free from nuclear weapons. To accept the status quo and abandon the ideal of peace maintained without military force is to threaten the very survival of the human race."
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At 8:15 AM on Aug 6, 1945, the U.S. B-29 warplane Enola Gay cast a bomb called "Little Boy" and decimated the city with an estimated population of 350,000. Thousands more died later from injuries and radiation-related illnesses.
On Saturday, as cicadas shrilled in the heavy summer air, the Peace Bell sounded, and the crowd, including Prime Minister Fumio Kishida, who is from Hiroshima, heeded with a moment of silence at the exact time the bomb exploded.
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"At the start of this year, the five nuclear-weapon states issued a joint statement: 'Nuclear war cannot be won and must never be fought,'" Matsui added.
"Why do they not attempt to fulfill their promises? Why do some even hint at using nuclear weapons?"
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On Thursday, Russian ambassador to Japan Mikhail Galuzin offered flowers at a memorial stone in the park and told reporters his nation would never use nuclear weapons.
Kishida, who has selected Hiroshima as the site of next year's Group of Seven summit, called on the world to renounce nuclear weapons.
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Earlier this week, he became the first Japanese leader to take part in the Review Conference of the Parties to the Treaty on the Non-Proliferation of Nuclear Weapons (NPT).
"We will continue towards the ideal of nuclear disarmament even given the current tough security environment," he said.
The Hiroshima catastrophe was followed by the U.S. military's atomic bombing of Nagasaki on Aug 9, immediately killing more than 75,000 people. Japan surrendered six days later, ending World War Two.